The four levels of protein structure

This unit explains the basic principles of protein structure. A number of examples are dealt with in an interactive way, including 3-dimensional detail in accompanying files.
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Primary structure 

Each protein is built up from a set number of amino acids, joined and shaped in a particular way.

There are 20 different types of amino acids, so for a simple dipeptide there are 400 possible combinations;  8000 combinations for a tripeptide.
Clearly the number of possible combinations is almost infinite when larger numbers of amino acids are combined to form a polypeptide.

The primary level of protein structure is not just the number and identity of the component amino acids in the protein, but the order or sequence in which the specific amino acids are combined (by condensation, forming peptide bonds) in the polypeptide chain.

Secondary structure

The polypeptide chain can fold back on itself in a number of ways. Each bond in the backbone formed by alternating amino acid central carbons and -CONH - peptide linkages can rotate completely, and so a number of shapes are possible.
It will become stabilised in a position where >NH groups (from the peptide bonds) become close enough to form hydrogen bonds with  >C=O groups on another peptide bond, in another chain, or further along in the same chain.

Often, these weak interactions between several successive amino acid residues result in a coiled (helical) structure.
The usual way in which the polypeptide chain is coiled is called the alpha helix, in which interactions take place between groups 3 - 4 amino acid residues apart. Some amino acids put a kink or bend in these regions of helical structure, allowing the chain to bend back on itself and form a more globular molecular structure.

Sections of alpha-helix are often seen in larger molecules, amongst other sections of polypeptide chain which are not so ordered. Some short proteins are practically all arranged as an alpha helix. An example is glucagon.

Do not get the alpha helix confused with the double helix of DNA, or the helix formed in sections of carbohydrate molecules (e.g. amylose, amylopectin, glycogen). And do not confuse it with alpha 1,4 and 1,6  glycosidic bonds formed in those compounds!

Other types of helical structure are sometimes seen in proteins.

The beta pleated sheet is another regular secondary structure, as seen in the protein fibroin in silk, which is composed of polypeptides - long chains of amino acids - running alongside one another.
These amino acids - mostly glycine, alanine and serine - have small R groups so the side chains fit together easily and allow many long straight parallel fibres to be formed, each facing in the opposite direction to the ones above and below.

Tertiary structure

The 3-dimensional structure of a protein's polypeptide chain or chains may be locked in place by other stronger bonds. These bonds are formed between components of  the -R groups of the amino acid residues. The types of bonds may include:
The tertiary level of protein structure is essentially responsible for the overall shape of the protein molecule, which is reflected in its function. For instance enzymes are mostly globular in shape, often with a cleft to expose the active site. Amylase and pepsin are examples.
Structural proteins, e.g.collagen, are often fibrous, composed of strands.

Quaternary structure

Not all proteins have a quaternary level of structure.

A protein with a quaternary structure consists of more than one (often practically identical) polypeptide sub-units, generally not joined by strong bonds like those above, but disulphide bridges between cysteines may be present.
A well known example is haemoglobin, which consists of 2 alpha and 2 beta chains, consisting of 141 and 146 amino acid residues respectively.
The hormone human chorionic gonadotrophin (hCG) has a quaternary structure, being composed of two polypeptide chains. Many enzymes consist of  several sub-units, often as dimers (2 sub-units) and tetramers (4 sub-units) combined in this way.

Do not assume that quaternary means "composed of 4 sub-units" because haemoglobin is composed of 4 sub-units. It is the 4th level of  protein structure.