Hi all so in my last post I was reflecting on proteins, and I left off at the different functions and types of proteins that there are. Today I will be continuing my reflection on proteins I do hope you enjoy!
Levels of protein structure!
Within a protein molecule there are four different levels of protein structure.
This refers to the exact sequence or linear sequence of amino acids in the polypeptide within a protein molecule. Only peptide bonds are involved in forming this sequence. Can you guess who was the first scientist to work out the primary structure of a protein?
It was this guy Frederick Sanger it took him ten years from (1944 – 1954) to analyse the structure of the protein, insulin.
At this level the polypeptide chain starts to fold, and the two most common types are alpha- helix and the beta- pleated sheets.
- The amino acid arrange themselves in a regular helical conformation
- The carbonyl oxygen of each peptide bond is hydrogen bonded to the hydrogen on the amino group, located four amino acids away. The hydrogen bonds run parallel to the axis of the helix.
- In an alpha helix there are 3.6 amino acids in each turn of the helix.
- The side chains which are the R – groups are all positioned along the outside of the cylindrical helix.
Alpha helix form more readily than many other conformations, why does happen?
It is due to the optimal use of the internal hydrogen bonds. Every peptide bond, except those on the end are involved in hydrogen bonding. Each successive turn of the helix is held to adjacent turns by 3 – 4 hydrogen bonds. When combined all the hydrogen bonds give the helical structure considerable stability.
Factors that affect alpha helices.
- There are some amino acids that are found less often in the alpha helices that others.
Proline for example , in the structure of proline and if you read my previous blog post on amino acid you would have seen the structure of proline, the nitrogen atom is involved in a ring structure and rotation about this N-C bond is not possible. This means that Proline forms a destabilizing kink in an helix.
It also cannot form the correct pattern of hydrogen bonds due to the lack of hydrogen atom.
Because of these reasons proline is found at the end of an alpha helix, where it alters the direction of polypeptide chain and terminates the helix.
Glysine is another amino acid that less often found in the alpha helices.
- Interactions between the amino acid side chains can either stabilize or destabilize the structure. Due to the long stretches of negative or positive charges they will repel each other , and this in turn prevents formation of the alpha helix.
- When there are large bulky side chain next to each other it can result in steric interference, this can prevent the formation of alpha helices.
- It is the twist of the of an alpha helix that ensures the correct interactions take place. Positively charged amino acids are often found 3 residues away from negatively charged amino acids, this permits the formation of an ion pair. Two aromatic amino acid residues are often similarly spaced, resulting in a hydrophobic interaction.
- The final factor Is the identity of the amino acid towards the end. At each of peptide bonds there are small electric dipoles, which are connected to each other via hydrogen bonding. This results in a net dipole along the helix, and it increases with length. The negatively charged residue is found at the amino terminal end and interacts with the positive charge, stabilizing the structure. The positively charged residues, are found at the carbonyl end and they stabilize the negative end of the helix dipole.
Because of the dipole associated with each hydrogen bond, and because they are aligned parallel the alpha helix has a large macrodipole which is positive at the N-terminal end.
The helices prefer to interact in an antiparallel manner so that their macrodipole interact favourably.
Beta- pleated sheets.
This form of secondary structure is much more simpler than that of the first one we looked at. Hydrogen bonds would form between the peptide bonds either in different polypeptide chains or in different sections of the same polypeptide chain.
It is the planarity of the peptide bonds that forces the polypeptide to be pleated with the side – chains of the amino acids protruding above and below the sheet.
This refers to the shape taken up by the polypeptide chains as a result of various bonds formed between parts of the R- groups of the chains.
Myoglobin is a water soluble , globular protein, the main driving forces behind the folding of the polypeptide chain is the energetic requirement to bury the non polar amino acid in the hydrophobic interior away from the surrounding aqueous, hydrophilic medium.
Once the polypeptide chain is folded, the 3D biologically – active conformation is maintained not only by hydrophobic interactions, but also by electrostatic forces, hydrogen bonds and even covalent disulfide bonds.
- Called the hydrophobic effect it is the name given to forces that can cause non polar molecules to minimize their contact with water
- It can be seen with amphipathic molecules such as lipids and detergents that form micelles in aqueous solutions
- In proteins their non polar side chains are out of contact with aqueous solvent, this means that the hydrophobic forces are very important in determining the structure , folding and stability of the proteins.
- In biological systems the donor group is either an oxygen or nitrogen which is covalently attached to a hydrogen atom, the acceptor being either an oxygen or nitrogen
- These hydrogen bonds are in the range of .27nm – .31nm and are highly directional , which means that the donor hydrogen and acceptor atoms are collinear.
- They are stronger than van der Waals forces bur weaker than covalent bonds.
- They play an important part in protein structure, also in the structure of other biological macromolecules, such as DNA double helix and lipid bilayers.
- It is also critical to both the properties of water and to its role as a biochemical solvent
- Interactions between two ionic groups of opposite charge, example the ammonium group of lys and the carboxyl group of asp
- It is often referred to as an ion pair or salt bridge.
- Involves the lost of H+ in an oxidation reaction
- This refers to how many polypeptide chains are present in a protein molecule and how they are linked together.
- In this fourth level of structure there are two types of interactions , covalent links ( eg. Disulfide bonds) and non covalent interactions ( eg. Electrostatic forces, hydrogen bonding, hydrophobic interactions)
- The quaternary structure prolongs the life of a protein, for example oligomers are more stable than their dissociated subunits.
References : AS Level Biology by Phil Bradfield , John Dodds, and Norma Taylor