Are There Rules for How Proteins Are Formed?

Are There Rules for How Proteins Are Formed?

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Proteins are formed by stringing together different amino acids. Different amino acids have different properties (such as being attracted to or repelled by water, positively or negatively charged, large, small, etc.).

What I would like to know is if there are any rules or principles which determine how amino acids are strung together to form proteins? If so, what are those rules and can anyone recommend any resources where I can learn more about this subject?



Let me try and explain what I am trying to ask. I understand that there are rules of grammar that I need to follow in order to put together a well formed English sentence. I am wondering if there is something akin to that for stringing together amino acids in order to create a 'well-formed' protein. (I am NOT referring to how DNA codes for amino acids).

For instance, imagine that I wanted to create a new protein and I had a pile of amino acids at my disposal. It seems to me that if I understood the principles and rules by which amino acid chains work then I could know which amino acids to string together and the order in which to string them together in order to create the particular type of protein that I wish to create.

This is similar to how I can string together letters and words to form well formed sentences or how I can string together well-formed sentences to create logical arguments. There's a logic to how to form a sentence and a different logic for how to form an argument -- and it is possible to discern that logic by studying syntax and reasonable arguments.

I assume the same is true for proteins. There must be some sort of logic or system for how amino acids are strung together -- some sort of connection between the 3-dimension, functional protein and the nature of the properties of the individual amino acids and how they are organized together. What I am wondering is whether or not we have any idea what that system of logic is.

It sounds like your question is "what are the rules to protein folding?"

That's not the only way to read your question.

Protein Folding is a unique problem - a 1D sequence maps to a 3D object. Since proteins mediate nearly all biochemical transformations and therefore mediate life's processes, protein folding one of the great unsolved problems in science today.

You can see in the example folded structure above there are helices and flat sheets of connected strands. You can see below in the schematic alpha beta barrel motif of triose phosphate isomerase (TIM) how elegant these structures can be.

Although the combinations and overall organization of the beta sheets and the alpha helices are boundless, there are some unifying motifs in these structures.

Long ago, a couple of researchers tabulated the amino acids probability of being in alpha helices or beta strands. The Chou-Fasman model is important in that it has approximately ~70% chance of detecting alpha helices and beta strands. Its not a great accuracy but what's really amazing about these algorithms is that they show that local forces - the interaction of amino acids near each other in the sequence have something to do with the formation of at least alpha-helices and beta strands.

There have been pounds worth of papers written since then. In general, statistical surveys of protein sequences have been able to identify folds or motifs by a long list of string and machine learning algorithms. Hidden Markov Models and Bayesian profiles are popular. Of course all these are similar to Chou-Fasman in that they work on the sequence in short segments more or less.

For a while it was thought that molecular dynamics and other discrete simulations might help to solve protein folding by allowing long distance interactions to be involved. Just simulating the entire protein molecule in a computer program as it moves into a folded conformation, but this has not proven to be possible for a couple of reasons: (1) it takes a long time for a protein to fold relative to the length of a tractable simulation (2) the forces involved in protein folding and molecular size scales are not really easy to simulate - they do not precisely simulate the forces and behavior experienced by molecules and they involve many more solvent molecules than most computations can involve - even today's server farms would get clogged up with respectable protein folding simulation.

Since 1994 the Critical Assessment of Structure Prediction (CASP) have provided an open competition every 2 years where 3D structures that have been determined experimentally is held from publication. While its well attended a new class of algorithms showed up around 2000. These algorithms work on the assumption that local forces are important to protein folding, but often incorporating molecular dynamics. Using MD or statistics based on protein structures (see the RCSB for the repository), segments of the protein sequence are tested for structural tendencies. chaining these predictions together, initial protein folds are put together. Once put together long term interactions can assemble a protein structure.

BTW that is not to say that Protein folding is solved - the solutions that come out often produce a structure that is really similar to the final structure, but often there are substantial differences.

Just looking at the individual sequence there are no simple rules to decide how the protein fold - ultimately molecular physics of the individual sequence determines where the fold will go.

This is incredibly terse, but it could get you started. Study of protein without any helices or beta strands is a topic in itself - they can be treated the same way as above. Then there are also proteins who do not have a single fold, but are dynamic and flop around all the time, or only have a shape when in contact with a surface of some kind. So there's even more.

Disclaimer: This is an interesting question if I have understood what you are trying to ask. But unfortunately the case is that there are so many different cases its impossible to cover them here. Other answers talk about folding and modification, but these are still heavily dependant on the "2d" DNA sequence and aren't useful if all one has is a final protein, so I'll discuss the 'rules' of a final structure. This started as a comment and got too long!

In summary, no, there are not many examples in the grand scheme of things where rules at a protein level exist in any sort of grammatical way. Its all about 3D chemistry.

Protein Structure in relation to Function.

Functional areas in a protein are often made up of structures like alpha helices and beta sheets linked by very flexible looping regions. The way these structural elements are connected is generally different in every protein. However some motifs that perform similar tasks can be identified by their 3D shape and order of connection (which I think is what you're asking about). For example the OB motif (images and good starting point here) has a strict order that the beta sheets follow, whereas the helix is optional. Although this is a neat example of protein "grammar", its very much exceptional when motifs like this are identified.

No Obvious Rules.

This following answer is educated guessing, and other peoples comments would be helpful.

Proteins are much more complex than a 2 dimensional language like English or DNA. One way to think about why your question is difficult to answer is considering that protein biochemistry happens in 3D space whereas our other examples, language and DNA, operate linearly in a 2D line.

Any evidence of a linear ordering in a finished protein implies very simple folding and post-translational processing. Most biochemical tasks are not simple and require complex nuances in the enzymes' chemistry (which comes from 3D chemistry, not 2D sequence). DNA is complicated too, but like our language, it is designed to be simple and read quickly in a line. This means if a sequence wants to do something a bit more sophisticated, it needs a specific order. This isn't a problem in 3D space as there is a lot more to variation other than sequence.

I'm going to assume that you mean "are there any rules for which amino acids can follow which amino acids in a protein?" The answer is no. In terms of a protein's chemistry, there is no restriction on the amino acid sequence.

However, not all amino acid sequences will fold into a definite 3D structure, and not all amino acid sequences will be soluble in water. For these reasons some amino acid sequences cannot be produced via the standard in vivo process (i.e. by a ribosome), but there's no reason they couldn't be produced through chemical synthesis.

I suppose you are not asking how does DNA code for mRNA which has codons (sets of 3 nucleic acids) when read in the correct reading frame (where 3 base pairs each are read beggining from the start codon) a ribosome then translates this into protein… theres a lot more details then what I said… that is called translation:

Afterwords the protein is folded into a 3d shape

Other stuff (other than amino acids) can be added, like a a lipid for anchoring into the membrane (GPI anchor or prenylation) or sugar (glycosylation) amoung other things, this is called post translational modification.

if you are asking about the evolution of proteins, here is another article:

wikipedia can get pretty detailed, also there might not be a lot of pictures… lippincott's illustrated biochemistry has lots of great pictures… but it's a book for health science students, not very abstract/theoretical/philosophical so you won't get much on evolution of protein families among different life forms…

If you are asking which amino acids can go together and which stuff can't, I dunno, I'm not a biochemist…

I hope that I got what are you asking. You give the example of words, it's not good one. Look on the protein like a machine or maybe cupboard. You bought one in Ikea and now you need to follow the instruction to bring together all the elements. If you just paste together all the parts you will not get a working cupboard. What rules the parts of cupboard following? Physic.
Take for beginning the Bohr model of atom. If you want simpler example - planets in solar system. After that put 10 atoms together to from the simplest amino acid. What structure will they get? Bring near another amino acid. How will they interact together?
The rules comes from physics. And they are very very very very complected. To understand what structure some protein will get or how it will interact with another protein - you need to take all the atoms in the system and to know how they will act one with another. Only huge computers can calculate such things - and only the simplest of them.

Edit: answer to the comment:
Thats what so amazing in the nature. The evolution found the way to build all the body proteins just from approximately 20 amino acids. By the way that doesn't mean that there is just 20 a.c. There are more that 500. 240 Of them can be found free in nature and other only only as intermediates in metabolism. (
If you want another example - take Lego. You have - lets say - 20 types of different peaces but you can make a lot of different things from them.
The nature must use a minimal amount of building blocks. This giving advantage in the evolution cause it is simpler. Look at the DNA. Its build just from 4 building blocks! And caring all the information of how to form entire body. Isn't it amazing? :)

DNA and Proteins

What is DNA?
DNA stands for deoxyribonucleic acid, and it is the carrier of genetic information within a cell. A molecule of DNA consists of two chains that are wrapped around each other. The chains twist to form a double helix in shape. Each chain is made up of repeating subunits called nucleotides that are held together by chemical bonds. There are four different types of nucleotides in DNA, and they differ from one another by the type of base that is present: adenine (A), thymine (T), guanine (G), and cytosine (C). A base on one of the chains that makes up DNA is chemically bonded to a base on the other chain. This bonding holds the two chains together. Additionally, there are base pairing rules that determine which bases can bond with each other. Adenine and thymine form base pairs that are held together by two bonds, while cytosine and guanine form base pairs that are held together by three bonds. Bases that bond together are known as complementary.

How DNA Encodes for Proteins:

1. Transcription: DNA to mRNA

During transcription, DNA is converted to messenger RNA (mRNA) by an enzyme called RNA polymerase. RNA is a molecule that is chemically similar to DNA, and also contains repeating nucleotide subunits. However, the “bases” of RNA differ from those of DNA in that thymine (T) is replaced by uracil (U) in RNA. DNA and RNA bases are also held together by chemical bonds and have specific base pairing rules. In DNA/RNA base pairing, adenine (A) pairs with uracil (U), and cytosine (C) pairs with guanine (G). The conversion of DNA to mRNA occurs when an RNA polymerase makes a complementary mRNA copy of a DNA “template” sequence. Once the mRNA molecule has been synthesized, specific chemical modifications must be made that enable the mRNA to be translated into protein.

2. Translation: mRNA to protein

During translation, mRNA is converted to protein. A group of three mRNA nucleotides encodes for a specific amino acid and is called a codon. Each mRNA corresponds to a specific amino acid sequence and forms the resultant protein. Two codons, called start and stop codons, signal the beginning and end of translation. The final protein product is formed after the stop codon has been reached. A table called the genetic code can be referred to in order to see which codons encode for which specific amino acids. Several of the codons end up encoding for the same amino acid, a process that is referred to as redundancy in the genetic code.

Types and Functions of Proteins

Proteins perform essential functions throughout the systems of the human body. These long chains of amino acids are critically important for:

  • catalyzing chemical reactions
  • synthesizing and repairing DNA
  • transporting materials across the cell
  • receiving and sending chemical signals
  • responding to stimuli
  • providing structural support

Proteins (a polymer) are macromolecules composed of amino acid subunits (the monomers ). These amino acids are covalently attached to one another to form long linear chains called polypeptides, which then fold into a specific three-dimensional shape. Sometimes these folded polypeptide chains are functional by themselves. Other times they combine with additional polypeptide chains to form the final protein structure. Sometimes non-polypeptide groups are also required in the final protein. For instance, the blood protein hemogobin is made up of four polypeptide chains, each of which also contains a heme molecule, which is ring structure with an iron atom in its center.

Proteins have different shapes and molecular weights, depending on the amino acid sequence. For example, hemoglobin is a globular protein, which means it folds into a compact globe-like structure, but collagen, found in our skin, is a fibrous protein, which means it folds into a long extended fiber-like chain. You probably look similar to your family members because you share similar proteins, but you look different from strangers because the proteins in your eyes, hair, and the rest of your body are different.

Figure (PageIndex<1>): Human Hemoglobin: Structure of human hemoglobin. The proteins&rsquo &alpha and &beta subunits are in red and blue, and the iron-containing heme groups in green. From the protein data base.

Because form determines function, any slight change to a protein&rsquos shape may cause the protein to become dysfunctional. Small changes in the amino acid sequence of a protein can cause devastating genetic diseases such as Huntington&rsquos disease or sickle cell anemia.

Covalent Bonds

Another type of strong chemical bond between two or more atoms is a covalent bond. These bonds form when an electron is shared between two elements and are the strongest and most common form of chemical bond in living organisms. Covalent bonds form between the elements that make up the biological molecules in our cells. Unlike ionic bonds, covalent bonds do not dissociate in water.

Interestingly, chemists and biologists measure bond strength in different ways. Chemists measure the absolute strength of a bond (the theoretical strength) while biologists are more interested in how the bond behaves in a biological system, which is usually aqueous (water-based). In water, ionic bonds come apart much more readily than covalent bonds, so biologists would say that they are weaker than covalent bonds. If you look in a chemistry textbook, you’ll see something different. This is a great example of how the same information can lead to different answers depending on the perspective that you’re viewing it from.

The hydrogen and oxygen atoms that combine to form water molecules are bound together by covalent bonds. The electron from the hydrogen atom divides its time between the outer shell of the hydrogen atom and the incomplete outer shell of the oxygen atom. To completely fill the outer shell of an oxygen atom, two electrons from two hydrogen atoms are needed, hence the subscript “2” in H 2 O. The electrons are shared between the atoms, dividing their time between them to “fill” the outer shell of each. This sharing is a lower energy state for all of the atoms involved than if they existed without their outer shells filled.

There are two types of covalent bonds: polar and nonpolar. Nonpolar covalent bonds form between two atoms of the same element or between different elements that share the electrons equally. For example, an oxygen atom can bond with another oxygen atom to fill their outer shells. This association is nonpolar because the electrons will be equally distributed between each oxygen atom. Two covalent bonds form between the two oxygen atoms because oxygen requires two shared electrons to fill its outermost shell. Nitrogen atoms will form three covalent bonds (also called triple covalent) between two atoms of nitrogen because each nitrogen atom needs three electrons to fill its outermost shell. Another example of a nonpolar covalent bond is found in the methane (CH 4 ) molecule. The carbon atom has four electrons in its outermost shell and needs four more to fill it. It gets these four from four hydrogen atoms, each atom providing one. These elements all share the electrons equally, creating four nonpolar covalent bonds (Figure 3).

In a polar covalent bond , the electrons shared by the atoms spend more time closer to one nucleus than to the other nucleus. Because of the unequal distribution of electrons between the different nuclei, a slightly positive (δ+) or slightly negative (δ–) charge develops. The covalent bonds between hydrogen and oxygen atoms in water are polar covalent bonds. The shared electrons spend more time near the oxygen nucleus, giving it a small negative charge, than they spend near the hydrogen nuclei, giving these molecules a small positive charge.

Figure 3 The water molecule (left) depicts a polar bond with a slightly positive charge on the hydrogen atoms and a slightly negative charge on the oxygen. Examples of nonpolar bonds include methane (middle) and oxygen (right).

Tertiary structure

The protein tertiary structure refers to the overall 3D structure of the polypeptide chain. This level of structure is principally due to the properties and interactions between the side chains of the amino acids, and depends on the nature of the chemical groups present on each amino acid. The properties of these side chains can attract or repel interactions with other side chains.

These interactions occur primarily through non-covalent bonds such as hydrogen and ionic bonds. Disulphide bonds are a unique example of a covalent bond that can form part of a tertiary structure, acting as strong bridges that form when two amino acids contain sulphur groups in their side chains. These stable bonds hold the tertiary structure in place.

Explain what the stages of protein folding are and how the protein is held in its 3D shape

Break this question down into the four stages: primary, secondary, tertiary and quarternary and for each one describe the structure and what the non-covelant interactions are that hold the protein together. Make sure your sentences are clear and concise, not waffley!

There are four stages of protein folding, primary, secondary, tertiary and quarternary.

The primary structure is the sequence of amino acids held together by peptide bonds

The secondary structure is the protein beginning to fold up. It can have two types of structure: the alpha helix, a coil shape held by hydrogen bonds in the same direction as the coil. The beta pleated sheet is an S shape pattern, also with hydrogen bonds holding the structure together. The hydrogen bonds are between NH and CO groups on the peptides.

The tertiary structure is the protein folded into its precise 3D structure, relating to the functon. This is held together by a range of non-covelant interactions between side groups, including ionic interations, disuplhide bridges, hydrophobic interactions, Van der Waals forces and hydrogen bonds.

The quarternary structure is when single peptides bond to other peptides, for example in haemoglobin.

Are There Rules for How Proteins Are Formed? - Biology


This page explains how amino acids combine to make proteins and what is meant by the primary, secondary and tertiary structures of proteins. Quaternary structure isn't covered. It only applies to proteins consisting of more than one polypeptide chain. There is a mention of quaternary structure on the IB chemistry syllabus, but on no other UK-based syllabus at this level.

Note: Quaternary structure can be very complicated, and I don't know exactly what depth the IB syllabus wants for this (which is why I haven't included it). I suspect what is wanted is fairly trivial. IB students should ask the advice of their teacher or lecturer.

The primary structure of proteins

Drawing the amino acids

In chemistry, if you were to draw the structure of a general 2-amino acid, you would probably draw it like this:

However, for drawing the structures of proteins, we usually twist it so that the "R" group sticks out at the side. It is much easier to see what is happening if you do that.

That means that the two simplest amino acids, glycine and alanine, would be shown as:

Peptides and polypeptides

Glycine and alanine can combine together with the elimination of a molecule of water to produce a dipeptide. It is possible for this to happen in one of two different ways - so you might get two different dipeptides.

In each case, the linkage shown in blue in the structure of the dipeptide is known as a peptide link. In chemistry, this would also be known as an amide link, but since we are now in the realms of biochemistry and biology, we'll use their terms.

If you joined three amino acids together, you would get a tripeptide. If you joined lots and lots together (as in a protein chain), you get a polypeptide.

A protein chain will have somewhere in the range of 50 to 2000 amino acid residues. You have to use this term because strictly speaking a peptide chain isn't made up of amino acids. When the amino acids combine together, a water molecule is lost. The peptide chain is made up from what is left after the water is lost - in other words, is made up of amino acid residues.

By convention, when you are drawing peptide chains, the -NH2 group which hasn't been converted into a peptide link is written at the left-hand end. The unchanged -COOH group is written at the right-hand end.

The end of the peptide chain with the -NH2 group is known as the N-terminal, and the end with the -COOH group is the C-terminal.

A protein chain (with the N-terminal on the left) will therefore look like this:

The "R" groups come from the 20 amino acids which occur in proteins. The peptide chain is known as the backbone, and the "R" groups are known as side chains.

Note: In the case where the "R" group comes from the amino acid proline, the pattern is broken. In this case, the hydrogen on the nitrogen nearest the "R" group is missing, and the "R" group loops around and is attached to that nitrogen as well as to the carbon atom in the chain.

I mention this for the sake of completeness - not because you would be expected to know about it in chemistry at this introductory level.

The primary structure of proteins

Now there's a problem! The term "primary structure" is used in two different ways.

At its simplest, the term is used to describe the order of the amino acids joined together to make the protein. In other words, if you replaced the "R" groups in the last diagram by real groups you would have the primary structure of a particular protein.

This primary structure is usually shown using abbreviations for the amino acid residues. These abbreviations commonly consist of three letters or one letter.

Using three letter abbreviations, a bit of a protein chain might be represented by, for example:

If you look carefully, you will spot the abbreviations for glycine (Gly) and alanine (Ala) amongst the others.

If you followed the protein chain all the way to its left-hand end, you would find an amino acid residue with an unattached -NH2 group. The N-terminal is always written on the left of a diagram for a protein's primary structure - whether you draw it in full or use these abbreviations.

The wider definition of primary structure includes all the features of a protein which are a result of covalent bonds. Obviously, all the peptide links are made of covalent bonds, so that isn't a problem.

But there is an additional feature in proteins which is also covalently bound. It involves the amino acid cysteine.

If two cysteine side chains end up next to each other because of folding in the peptide chain, they can react to form a sulphur bridge. This is another covalent link and so some people count it as a part of the primary structure of the protein.

Because of the way sulphur bridges affect the way the protein folds, other people count this as a part of the tertiary structure (see below). This is obviously a potential source of confusion!

Important: You need to know where your particular examiners are going to include sulphur bridges - as a part of the primary structure or as a part of the tertiary structure. You need to check your current syllabus and past papers. If you are studying a UK-based syllabus and haven't got these, follow this link to find out how to get hold of them.

The secondary structure of proteins

Within the long protein chains there are regions in which the chains are organised into regular structures known as alpha-helices (alpha-helixes) and beta-pleated sheets. These are the secondary structures in proteins.

These secondary structures are held together by hydrogen bonds. These form as shown in the diagram between one of the lone pairs on an oxygen atom and the hydrogen attached to a nitrogen atom:

Although the hydrogen bonds are always between C=O and H-N groups, the exact pattern of them is different in an alpha-helix and a beta-pleated sheet. When you get to them below, take some time to make sure you see how the two different arrangements works.

Important: If you aren't happy about hydrogen bonding and are unsure about what this diagram means, follow this link before you go on. What follows is difficult enough to visualise anyway without having to worry about what hydrogen bonds are as well!

You must also find out exactly how much detail you need to know about this next bit. It may well be that all you need is to have heard of an alpha-helix and know that it is held together by hydrogen bonds between the C=O and N-H groups. Once again, you need to check your syllabus and past papers - particularly mark schemes for the past papers.

If you follow either of these links, use the BACK button on your browser to return to this page.

In an alpha-helix, the protein chain is coiled like a loosely-coiled spring. The "alpha" means that if you look down the length of the spring, the coiling is happening in a clockwise direction as it goes away from you.

Note: If your visual imagination is as hopeless as mine, the only way to really understand this is to get a bit of wire and coil it into a spring shape. A bit of computer lead would do.

In truth, if you are a chemistry student, you are very unlikely to need to know this. If protein secondary structure is on your syllabus, your examiners are most likely only to want you to know how the structures are held together by hydrogen bonding. Check past papers to be sure.

If you are reading this as a biochemistry or biology student, and have been given some other way of recognising an alpha-helix, stick to whatever method you have been given.

The next diagram shows how the alpha-helix is held together by hydrogen bonds. This is a very simplified diagram, missing out lots of atoms. We'll talk it through in some detail after you have had a look at it.

What's wrong with the diagram? Two things:

First of all, only the atoms on the parts of the coils facing you are shown. If you try to show all the atoms, the whole thing gets so complicated that it is virtually impossible to understand what is going on.

Secondly, I have made no attempt whatsoever to get the bond angles right. I have deliberately drawn all of the bonds in the backbone of the chain as if they lie along the spiral. In truth they stick out all over the place. Again, if you draw it properly it is virtually impossible to see the spiral.

So, what do you need to notice?

Notice that all the "R" groups are sticking out sideways from the main helix.

Notice the regular arrangement of the hydrogen bonds. All the N-H groups are pointing upwards, and all the C=O groups pointing downwards. Each of them is involved in a hydrogen bond.

And finally, although you can't see it from this incomplete diagram, each complete turn of the spiral has 3.6 (approximately) amino acid residues in it.

If you had a whole number of amino acid residues per turn, each group would have an identical group underneath it on the turn below. Hydrogen bonding can't happen under those circumstances.

Each turn has 3 complete amino acid residues and two atoms from the next one. That means that each turn is offset from the ones above and below, such that the N-H and C=O groups are brought into line with each other.

In a beta-pleated sheet, the chains are folded so that they lie alongside each other. The next diagram shows what is known as an "anti-parallel" sheet. All that means is that next-door chains are heading in opposite directions. Given the way this particular folding happens, that would seem to be inevitable.

It isn't, in fact, inevitable! It is possible to have some much more complicated folding so that next-door chains are actually heading in the same direction. We are getting well beyond the demands of UK A level chemistry (and its equivalents) now.

The folded chains are again held together by hydrogen bonds involving exactly the same groups as in the alpha-helix.

Note: Note that there is no reason why these sheets have to be made from four bits of folded chain alongside each other as shown in this diagram. That was an arbitrary choice which produced a diagram which fitted nicely on the screen!

The tertiary structure of proteins

What is tertiary structure?

The tertiary structure of a protein is a description of the way the whole chain (including the secondary structures) folds itself into its final 3-dimensional shape. This is often simplified into models like the following one for the enzyme dihydrofolate reductase. Enzymes are, of course, based on proteins.

Note: This diagram was obtained from the RCSB Protein Data Bank. If you want to find more information about dihydrofolate reductase, their reference number for it is 7DFR.

There is nothing particularly special about this enzyme in terms of structure. I chose it because it contained only a single protein chain and had examples of both types of secondary structure in it.

The model shows the alpha-helices in the secondary structure as coils of "ribbon". The beta-pleated sheets are shown as flat bits of ribbon ending in an arrow head. The bits of the protein chain which are just random coils and loops are shown as bits of "string".

The colour coding in the model helps you to track your way around the structure - going through the spectrum from dark blue to end up at red.

You will also notice that this particular model has two other molecules locked into it (shown as ordinary molecular models). These are the two molecules whose reaction this enzyme catalyses.

What holds a protein into its tertiary structure?

The tertiary structure of a protein is held together by interactions between the the side chains - the "R" groups. There are several ways this can happen.

Ionic interactions

Some amino acids (such as aspartic acid and glutamic acid) contain an extra -COOH group. Some amino acids (such as lysine) contain an extra -NH2 group.

You can get a transfer of a hydrogen ion from the -COOH to the -NH2 group to form zwitterions just as in simple amino acids.

You could obviously get an ionic bond between the negative and the positive group if the chains folded in such a way that they were close to each other.

Notice that we are now talking about hydrogen bonds between side groups - not between groups actually in the backbone of the chain.

Lots of amino acids contain groups in the side chains which have a hydrogen atom attached to either an oxygen or a nitrogen atom. This is a classic situation where hydrogen bonding can occur.

For example, the amino acid serine contains an -OH group in the side chain. You could have a hydrogen bond set up between two serine residues in different parts of a folded chain.

You could easily imagine similar hydrogen bonding involving -OH groups, or -COOH groups, or -CONH2 groups, or -NH2 groups in various combinations - although you would have to be careful to remember that a -COOH group and an -NH2 group would form a zwitterion and produce stronger ionic bonding instead of hydrogen bonds.

van der Waals dispersion forces

Several amino acids have quite large hydrocarbon groups in their side chains. A few examples are shown below. Temporary fluctuating dipoles in one of these groups could induce opposite dipoles in another group on a nearby folded chain.

The dispersion forces set up would be enough to hold the folded structure together.

Important: If you aren't happy about van der Waals dispersion forces you should follow this link.

Use the BACK button on your browser to return to this page.

Sulphur bridges

Sulphur bridges which form between two cysteine residues have already been discussed under primary structures. Wherever you choose to place them doesn't affect how they are formed!

Questions to test your understanding

If this is the first set of questions you have done, please read the introductory page before you start. You will need to use the BACK BUTTON on your browser to come back here afterwards.

How to Break Proteins

Proteins are essential for all living things to function. They are large molecules made up of long chains of amino acids. Depending on the types of amino acids they have, proteins fold in very specific ways. The way they fold controls what the proteins are able to do. Proteins help move other molecules, respond to signals, make reactions happen more quickly, and replicate DNA, among other things. However, if proteins lose their specific folded shape, they are not able to work properly.

Proteins are long molecules that are twisted into a 3-Dimensional shape. That shape, based on the way they fold, is important to their function. If they lose that shape, they stop working properly. Click to enlarge.

Proteins require specific conditions to keep their shape. For example, most proteins in our bodies rely on us to keep a warm (but not hot) body temperature, stay hydrated, and take in enough of specific nutrients like salt. If our bodies aren’t able to maintain these conditions, some of our proteins may not function as well, or at all. Most organisms actually produce special proteins called “molecular chaperones” that help other proteins and molecules continue to work even if conditions are becoming difficult to tolerate.

When a protein is exposed to conditions too far outside of a range it can tolerate, that protein’s shape will come undone. This is called “denaturing” (basically, breaking) a protein. We denature proteins all the time when we cook food (think: eggs). In this activity, we will use common household products or processes to denature egg proteins in two main ways—by cooking them, and by exposing them to concentrated alcohol (ethanol). Do you think egg will look the same or different depending on how the proteins it holds are denatured?

  • Stove or microwave
  • Pot or microwave-safe container to boil water
  • 1 fork
  • 1 pair scissors
  • 1 bowl
  • 4 small glass containers of the same size
  • 1 egg (split egg white into four parts) additional can be used
  • 2/3 cup water (150 ml)
  • 1/3 cup of rubbing alcohol (75 ml)

Watch biologist Melissa Wilson Sayres as she shows you step-by-step how to break the proteins in egg whites.

Are There Rules for How Proteins Are Formed? - Biology

Tutorial to help answer the question

The tertiary structure of a protein refers to the:

A. Sequence of amino acids

B. Presence of alpha-helices or beta-sheets

C. Unique three dimensional folding of the molecule

D. Interactions of a protein with other subunits of enzymes

E. Interaction of a protein with a nucleic acid


It is convenient to describe protein structure in terms of 4 different aspects of covalent structure and folding patterns. The different levels of protein structure are known as primary, secondary, tertiary, and quaternary structure.
Primary Structure of Proteins
The primary structure is the sequence of amino acids that make up a polypeptide chain. 20 different amino acids are found in proteins. The exact order of the amino acids in a specific protein is the primary sequence for that protein.

Secondary Structure of Proteins

Protein secondary structure refers to regular, repeated patterns of folding of the protein backbone. The two most common folding patterns are the alpha helix and the beta sheet .
Alpha Helix
In an alpha helix, the polypeptide backbone coils around an imaginary helix axis in clockwise direction.

In this illustration, only the N-C-CO backbone atoms are shown. Note the coiling of the backbone around an imaginary axis down the center of the helix.

5 Major Stages of Protein Synthesis (explained with diagram) | Biology

Some of the major stages of Protein Synthesis are: (a) Activation of amino acids, (b) Transfer of amino acid to tRNA, (c) Initiation of polypeptide chain, (d) Chain Termination, (e) Protein translocation

There are five major stages in protein synthesis each requiring a number of components in E. coli and other prokaryotes.

Protein synthesis in eukaryotic cells follows the same pattern with some differences.

(a) Activation of amino acids:

This reaction is brought about by the binding of an amino acid with ATP. The step requires enzymes called amino acyI RNA synthetases. Due to this reaction amino acid (AA) and adenosine triphosphate (ATP), mediated by above enzyme, amino acyl – AMP – enzyme complex is formed (Fig. 6.40).

AA + ATP Enzyme -AA – AMP – enzyme complex + PP

It should be noticed that amino acyl RNA synthetases are specific with various amino acids.

(b) Transfer of amino acid to tRNA:

The AA – AMP – enzyme complex formed reacts with specific tRNA. Thus amino acid is transferred to tRNA. As a result the enzyme and AMP are liberated.

AA – AMP – enzyme Complex + tRNA- AA – tRNA + AMP enzyme

(c) Initiation of polypeptide chain:

Charged tRNA shifts to ribosome (Fig. 6.41). The ribosome consists of structural RNAs and 80 different proteins. Ribosome is the site where the protein synthesis occurs. The mRNA binds to SOS sub-unit of ribosome of 70S type.

It has already been discussed that ribosomes are made up of an rRNA (ribosomal RNA) and proteins. Ribosome also acts as a catalyst (23sRNA in bacteria is the enzyme— ribozyme) for the formation of peptide bond. Ribosomes consist of two subimits, a larger and a smaller one.

The information for the sequence of amino acids is present in the sequence of nitrogenous bases of mRNA. Each amino acid is coded for three letters word of nucleic acid. The initiation of polypeptide chain in prokaryotes is always brought about by the amino acid methionine which is regularly coded by the codon AUG but rarely also by GUG (for valine) as also initiating codon. In prokaryotes, formulation of initiating amino acid methionine is essential requirement.

Ribosomes have two sites for binding amino-acyl- tRNA.

(i) Amino-acyl or A site (acceptor site).

(ii) Peptidyl site or P site (donor site). Each site is composite of specific portions of SOS and 30S sub-units. The initiating formyl methionine tRNA i.e. (AA, f Met tRNA) can bind only with P site (Fig. 6.41).

However, it is an exception. All other newly coming amino-acyl- tRNAs (AA2, AA3 — tRNA) bind to A site. Thus, P site is the site from which empty tRNA leaves and to which growing peptidyl tRNA becomes bound.

In the first step, the next amino acyl-tRNA is bound to complex of elongation factor Tu containing a molecule of bound GTP the resulting amino-acyl-tRNA-Tu-GTP complex is now bound to the 70S initiation complex. GTP is hydrolysed and Tu-GDP complex is released form the 70S ribosome (Fig. 6.42). The new amino acyl tRNA is now bound to the amino acyl or A site on the ribosome.

In the second step of elongation, the new peptide bond is formed between the amino acids whose tRNAs are located on the A and P sites on the ribosomes. This step occurs by the transfer of initiating formyl methionine acyl group from its tRNA to the amino group of new amino acid that has just entered the A site.

The peptide formation is catalysed by the peptidyl transferase, a ribosomal protein in 50 S sub-unit. A dipeptidyl tRNA is formed on the A site and now empty tRNA remains bound to the P site.

In the third step of elongation, the ribosome moves along the mRNA towards its 3′ end by a distance of codon (i.e., 1st to 2nd codon and 2nd to 3rd on the mRNA). Since the dipeptidyl tRNA is still attached to second codon (Fig. 6.43), the movement of ribosomes shifts the dipeptidyl tRNA from A site to the P-site. This shifting causes the release of the tRNA which is empty.

Now the third codon of mRNA is on the A-site and the second codon on P-site. This shift of ribosomes along mRNA is called translocation step. This step requires elongation factor G (also called translocase). And also simultaneously the hydrolysis of another molecule of GTP takes place. The hydrolysis of GTP provides energy for the translocation.

The ribosome with its attached dipetidyl tRNA and mRNA is ready for another elongation cycle to attach the third amino acid (Fig. 6.44). It takes place in the same way as the addition of second.

As a result of this repetitive action for chain elongation, the polypeptide chain elongates. As the ribosome moves from codon to codon along the mRNA towards its 3′ end, the polypeptide chain of the last amino acid is to be inserted.

(d) Chain Termination:

The termination of polypeptide is signalled by one of the three terminal triplets (codons) in the mRNA. The three terminal codons are UAG (Amber), UAA (Ochre) and UGA (Opal). They are also called stop signals.

At the time of termination, the terminal codon immediately follows the last amino acid codon. After this, the polypeptide chain, tRNA, mRNA are released. The subunits of ribosomes get dissociated.

Termination also requires the activities of three termination or releasing factors named as R1, R and S.

(e) Protein translocation:

Two classes of poly­ribosomes have been identified (Fig. 6.45).

(ii) Membrane bound polyribosomes.

For free ribosomes, termination of protein synthesis leads to the release of completed protein into cytoplasm. Some of these specific proteins are translocated to mitochondria and nucleus by special type of mechanisms.

On the other hand in membrane bound polyribosomes, polypeptide chain which grows on mRNA is inserted into the lumen of ER membrane. Some of these proteins become integral part of the membrane.