Proteins- Levels of Structure

Now we've moved past from amino acids to proteins, which are larger structures made up of amino acids. Hopefully these next few posts should be at least marginally more interesting than those about amino acids.

Recognise that the linear sequence of bases in the coding strand of DNA code for the linear sequences of bases in mRNA which in turn codes for the linear sequence of amino acids in a protein polypeptide chain. 

I thought that this is something that I've covered earlier, but apparently not. The bases in the coding strand can be copied to messenger RNA in a process known as transcription. This mRNA then leaves the nucleus for the cytosol, where it is transcribed on ribosomes into an amino acid sequence. This amino acid sequence can then fold to create a protein.

Know which is the amino (N)-terminus and which is the carboxyl (C)-terminus of a polypeptide chain and how amino acids in a polypeptide chain are numbered starting from the N-terminus.

The amino terminus is the end with the amine group while the carboxyl terminus is the end with carboxylic acid group. As for numbering, I'm sure they're just numbered 1, 2, 3 etc. from N-terminus to C-terminus.

Understand that the polypeptide chain has to fold into a defined 3-D structure in order for the protein to be biologically functional.

As I'm fairly sure I've mentioned before, structure is critical to function as enzymes and so on function through the way that proteins and other molecules fit together. Hence, for a protein to be biologically functional, it needs to fold into its correct structure first.

Know how H-bonding between peptide bonds stabilises the helical structure, with bonding formed between one amino acid carbonyl oxygen and the amide proton of an amino acid 4 residues along the polypeptide chain, leading to 3.6 amino acid residues per turn. Especially note that the side chains of the amino acids face outwards from the helix and are not inside the helical structure where there is no room.

Know why an α-helix has a dipole.

The carbonyl oxygen has a slightly negative charge, while the amide proton has a slightly positive charge. These conditions allow hydrogen bonds to be formed between the carboxyl groups of amino acids with the amide groups of amino acids four residues away. This forms a helical structure known as an alpha helix (a common secondary structure of proteins). In the alpha helix, all of the carboxyl groups face in one direction whereas all the amine groups face in the other, as this helps with hydrogen bonding between residues. As such, alpha-helices have dipoles: a slightly negative end that contains more carboxyl groups, and a more positive end that contains more amine groups.

Know that H-bonding between peptide bonds on two segments of β-sheet stabilise the structure and what the terms parallel and antiparallel mean. Also, it is important to know that the amino acid side chains lie above and below the plane of the sheet.

Beta-sheets are different secondary structures of proteins. In beta sheets, you essentially have chains of amino acids lying side by side. These chains of amino acids are held together by hydrogen bonds between the carboxyl groups of some amino acids with the amide groups of other amino acids, just like in alpha-helices. Chains can be parallel if they are all running in the same direction (N-terminus to C-terminus) or antiparallel if every second one is running in the opposite direction. As stated in the dot point, amino acid side chains lie above and below the plane of the sheet. Due to the zig-zag bending of the chain due to bond locations etc., half of the amino acids lie above the sheet and the other half lie below.

Know what a β-turn is and where it is found and the reasons why Gly and Pro are often found in them.

A beta-turn is basically a small loop that connects two antiparallel strands of a beta sheet (parallel strands have a beta-loop instead, which is much bigger). As this requires quite a tight turn, glycine, which only has a hydrogen atom in its side chain, is often used so as not to interfere with the other closely-packed amino acids. Proline is also often used because its tight ring-structure forces the chain to turn sharply, especially when proline is in the cis-form.

Be able to define the angles Φ and Ψ and explain why some combinations angles of Φ and Ψ do not occur and why some combinations are favoured. Be able to relate this to the Ramachandran diagram which shows that common secondary structures fall in areas of highly favourable combinations of Φ and Ψ. 

Phi is the angle around the C-N part of the peptide bond, whereas psi is the angle around the C-C part of the peptide bond. Some angles are not allowed because they would bring the carboxyl groups or the amino groups too close to each other. A Ramachandran diagram is a diagram showing the sterically allowed values of phi and psi. As expected, commonly found structures contain favourable combinations of phi and psi.

Understand that pieces of secondary structure often combine into motifs that are components of the final tertiary structure of a protein, know a couple of examples that between them have α-helices and β-sheets as components.

As mentioned before, alpha-helices and beta-sheets are common secondary structures. These secondary structures can combine to form motifs, which can then combine further to form the overall tertiary structure of the protein. One of these motifs is the beta-alpha-beta motif, which is essentially two parallel strands of a beta-sheet, but the beta-loop is made up of an alpha helix. The beta-hairpin motif is essentially several antiparallel beta strands next to each other with beta-turns between them. There is also an alpha-alpha motif which consists of several alpha helices side by side. Alpha-helices and beta-sheets can also combine to form "barrels" through which other substances may be able to pass through, as in the case of pores and channels in the cell membrane. Common structures here are beta-barrels and alpha/beta-barrels. (Not sure if there are alpha-barrels.)

Understand the different graphical representations of models of protein structures.

Unfortunately I don't have any non-copyrighted pictures to show you, but proteins as displayed in textbooks etc. may be displayed in several different ways. Sometimes a ball-and-stick model is shown with every atom and every connection between them. Other times you might see alpha-helices displayed as cylinders or spirals and beta-sheets displayed as arrows, with thin tubes connecting them. There are several other ways that proteins might be displayed which I'm not going to go into here because it's kind of hard to explain without pictures.

Understand how the different levels of protein structure relate to each other.

Know the nomenclature of quaternary structures (subunits,α,β etc.) and how subunits bind to each other.

The primary level of protein structure is the amino acid sequence. The amino acid sequence, and the order of the side chains, affects the way that the protein will fold.

The secondary level of protein structure is the formation of alpha-helices and beta-sheets. This is facilitated by hydrogen bonds between the carboxyl and amino groups of the amino acids.

The tertiary level of protein structure is the combination of alpha-helices and beta-sheets into motifs and ultimately a completely folded polypeptide chain.

The quaternary level of protein structure is the association of several different polypeptide chains to form a protein. This doesn't happen for every protein- some proteins consist of only a single polypeptide chain. In proteins that do have multiple polypeptide chains, each polypeptide chain is called a subunit and is given a name such as alpha or beta. For example, haemoglobin has two alpha and two beta subunits. Subunits bind mostly through noncovalent interactions, such as hydrogen bonds, but sometimes interchain disulfide bonds do occur.