The constraints protein-protein interactions place on sequence divergence.

Structural analyses on a small number of protein families have shown that residues in protein interfaces are more conserved than average amino acid residues. This is also true of other ligand-binding and active site residues. This raises the question whether protein interactions place additional constraints on sequence divergence beyond this general background of functional restrictions on all different types of proteins. In order to investigate this, the sequence identities of Saccharomyces cerevisiae (SC) proteins to their Schizosaccharomyces pombe (SP) orthologues were used as a measure of sequence divergence. The SC proteins were divided into those in stable complexes, those that participate in transient interactions and the remaining proteins. All types of proteins can undergo extensive divergence: all three sequence identity distributions range from less than 20 to over 90%. However, overall, protein interactions do place additional constraints on sequence divergence and the distributions differ significantly: proteins not known to be involved in interactions have an average sequence identity of 38% while this value is 46% for proteins in stable complexes. Proteins that have transient interactions are intermediate between the two, with an average sequence identity of 41%. This trend is independent of whether the proteins are involved in informational functions (transcription, translation and replication) or not and of protein dispensability.