Conservation, Evolutionary

Locating Conserved PatchesLocating Conserved Patches

Patches of highly conserved residues on the surface of a protein molecular structure are good candidates for functional sites. These can be readily identified and visualized automatically with the ConSurf Server, provided a sufficient number of related protein sequences are in the Uniprot database.

(Need examples of ConSurf results in Jmol here)

Locating Variable PatchesLocating Variable Patches

In some cases, patches of highly variable (rapidly mutating) residues are also functional sites. These can also be identified with the ConSurf Server. For example, mutations in influenza hemagglutinin help the virus to evade host defenses. Another example is the high allelic variability of the peptide-binding groove of Major Histocompatibility Class I. That variability helps the grooves of the alleles within any individual to bind a wide range of peptides, hence enabling the T lymphocyte system to defend against a wide range of pathogens, including influenza virus.

Conservation for Domain FoldingConservation for Domain Folding

Certain residues on the surfaces of protein molecules tend to be conserved in order to maintain proper folding, rather than because they are part of a site functioning to interact with substrate, ligand, or a protein partner. Secondary structure elements need to break, in order to turn back into the folded protein domain, at the protein molecular surface. Therefore, it is common to see highly conserved residues that enable turns, or break helices, notably glycines or prolines, on protein structure surfaces.

Every structure in Proteopedia has a link to be displayed in FirstGlance in Jmol. There, you can use the Find dialog to enter the name of an amino acid, e.g. glycine or proline, and the positions of all of the specified amino acids will be highlighted. You can then visualize their distribution in the 3D structure.