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2Can Support Portal - Protein Structure
Building Blocks of Peptides and Proteins
There are 20 common amino acids. Peptides are small polymers of amino acids that bond together via a peptide bond to form a chain. Proteins are large polymers, such as enzymes, that are actively involved in the biological reactions of living organisms. Other kinds of proteins play a structural role in the cell. They are the building bricks of cell walls, cell membranes or are globular proteins within the cytoplasm.
All amino acids have an amino group, a carboxyl group and a variable side group, denoted as NH3, COOH and R, respectively. Amino acids bind together via peptide bonds, which occur between the amino and carboxyl groups of adjacent amino acids. The variable side group is the most important as its distinctive physio-chemical properties dictate the angle at which the peptide bond occurs and this dictates the folding of the protein.
Depending on their overall electrostatic charge, amino acids can be subdivided into the following 3 groups: Polar, non-polar and charged. Polar and charged amino acids will most often be found at the surface of proteins. They interact with the surrounding environment. Non-polar amino acids are more often found in the inside of proteins, buried, where they may play an active role in the function of the protein.
Primary
The final product of the DNA/RNA translation machinery is a product that contains between 10 and 10,000 amino acids linked in a single polymer. This one is often referred to as the primary protein sequence. The order in which the amino acids appear in this sequence determines the structure of a protein and alteration to this order is called a mutation and may result in the loss of function of the protein.
Understanding the structure of proteins is central in understanding how these interact with each other and with other structures of living cells. For example, knowing how a protein is arranged in the cell membrane (which is composed mainly of lipids (fat) molecules) helps us to understand how they work and can lead to understanding not only the cause, but also eventually to the cure for virus infections, such as the common cold. Another example is in a serious disease such as cystic fibrosis where a change in a gene for a transmembrane conductance regulator, characterised by the loss of three thymines, leads to a phenylalanine missing in the primary protein sequence of the product (at position 508). A protein is made which is non functional. This loss of function leads to the inability to clear secretions from a variety of organs.
We are still a long way from being able to make an accurate model of a complete bacterial, let alone a eukaryotic cell. However, there are over 40,000 structures for which the three-dimensional coordinates are known. These structures are stored in a database known as PDB (Protein Databank), which is maintained by the
PDBe group at the EBI in collaboration with RCSB. The database comprises DNA/RNA, carbohydrates, individual proteins and models of macromolecular complexes as well as simple viruses.
Basic Secondary Structures of Proteins
 As previously stated, the order in which amino acids occur in proteins is determined by the genetic code. The surrounding chemical environment, which is primarily composed of water (and other solvents) at different concentrations and temperatures, and the amino acid side chains, determine the way in which these are arranged in space relative to each other. In other words, amino acid chains do not fold at random. The basic structures that form are known as sheets (beta-sheets), helices (alpha-helices) and turns. These are also known as basic Secondary Structures.
An alpha helix resembles a ribbon wrapped around a tube, similar to a circular staircase. This structure is very stable but flexible therefore it is often seen in parts of a protein that need to bend or move.
In a beta-sheet, two or more ribbons of amino acids are involved. These line up to form a pleated like structure similar to folds in fabric. This structure tends to be rigid and less flexible than alpha helices.
See
picture above of the protein dihydrofolate reductase.
During and after protein synthesis, a protein folds into alpha helices and beta sheets. These areas of secondary structure bind together and fold on each other in specific ways. Once the process of protein synthesis is completed, the protein takes its final shape. This stable form of the protein is know as the mature form, also known as the tertiary structure.
 Cysteine is perhaps the most important amino acid as it is the only one with an S-H (or sulfhydryl) group. Sulfhydryl groups interact with each other to form disulphide bridges (-S-S-) that link neighbouring cysteines and thus bring closer the amino acids chains where they occur, see picture on the right.
Turns are usually related to proline and glycine, which are common and small and are often responsible for sharp bends and twists in alpha helices and hair-pins in beta sheets. By knowing which spatial geometry neighbouring amino acids adopt when they bind together it is possible to determine which secondary structure a protein may have.
Alpha helices and beta sheets are subdivided into classes that extend the basic definitions given here. There are also wide helices, which appear along short segments of proteins. Beta sheets are subdivided into anti-parallel and parallel sheets. Beta stands are also common where a sheet is not formed and turns of various types. Barrels, loops and coils are also found and denote specific regions, which are found in proteins as units.
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