Most proteins which occur in the aqueous, intracellular environment or in the plasma are of globular nature: they are very approximately spherical in shape, or consist of several different lobes (domains). Generally, proteins with more than about 200 amino acid residues are multi-domain (although there are exceptions). The different domains of a single protein may be responsible for quite different functions. This is taken to extremes in a number of 'modular' proteins, which are mostly extracellular and glycosylated (see section on mosaic proteins).
The tertiary structure of globular proteins reflects their interaction with their aqueous solvent. At a simple level, a globular protein may be considered to consist of a hydrophobic core surrounded by a hydrophilic external surface which interacts with water. The tertiary fold of the polypeptide is such that those residues with apolar side chains are buried in the centre, while the polar residues remain exposed. This principle is held by many to be the dominant driving force behind the folding of the polypeptide chain into the compact globular form: the aggregation and burial of the hydrophobic surface reduces the number of unfavourable interactions of these groups with water; thus the hydrophobic effect. (A section on this will be released in due course.)
Compare this distribution of hydrophilic and hydrophobic side chains with that in an integral membrane protein (see the relevant page).
Bear in mind however that although the concept of "hydrophobic residues in, polar residues out" generally applies, it has its limitations. Residues with hydrophobic side chains have some polar surface area (the backbone atoms), and vice versa. There will necessarily be some buried polar groups in the hydrophobic interior (generally main chain atoms involved in hydrogen bonding in secondary structures). Likewise, the amount of solvent-exposed hydrophobic surface area is far more than minimal: in fact it constitutes approximately 50% of the total exposed surface area of a globular protein. A patchwork arrangement of hydrophobic and polar surface allows solvent molecules close to apolar regions to interact favourably with neighbouring polar surfaces.
PPS Consultant Simon Brocklehurst describes Side-chain Packing in Hydrophobic Cores.
Globular proteins are more likely to crystallize than membrane proteins, or fibrous proteins. As a result, the great majority of solved structures are globular.
X-Ray diffraction is the technique most used, and which we use at Birkbeck. That will be the subject of `another course'.
Another important technique for elucidating protein structure is NMR Spectroscopy:
Last updated 7th April '97