BP03 From the primary to the quaternary structure

A protein has a complex three-dimensional structure that is built up in four levels. Three of these (primary, secondary and tertiary structure) are common whilst the fourth level (quaternary structure) requires the protein to contain more than one polypeptide chain.

Primary structure
Proteins are polymers with a specific number and order of amino acids. This order, passed on by the genetic code, is called the primary structure and is the basis for the further folding of the protein chain.

Secondary structure
A protein chain is not a linear molecule: locally the chains fold themselves in a specific manner. The alpha helix is an example of this regular folding. Hydrogen bonds play an important role in the stabilisation of this secondary structure.

Tertiary structure
Helix domains can in turn fold to give a complex structure.
In myoglobin eight alpha helix domains are folded around a central heme group (coloured green on the illustration). Chiefly non-covalent interactions such as electrostatic forces, hydrogen bonding, and dipole-dipole interactions contribute to the stability of the tertiary structure.

Quaternary structure
Proteins can sometimes exist in the cells as aggregates of two or more folded polypeptide chains called sub-units. Haemoglobin is for example built up of four folded chains, each of which has a structure analogous to that of myoglobin.

The prediction of the three-dimensional structures of proteins, via computer simulation based on the primary structure, is still a dream for most proteins, although it is usually possible to do this for the secondary structure. When the protein can be crystallised however it is possible to determine the three-dimensional structure experimentally using X-ray diffraction. An important part of our knowledge of the three-dimensional structure and the structure-activity relationships of proteins is based on this technique.