Protein-protein interactions; coupling of structurally conserved residues and of hot spots across interfaces. Implications for docking.
Hot spot residues contribute dominantly to protein-protein interactions. Statistically, conserved residues correlate with hot spots, and their occurrence can distinguish between binding sites and the remainder of the protein surface. The hot spot and conservation analyses have been carried out on one side of the interface. Here, we show that both experimental hot spots and conserved residues tend to couple across two-chain interfaces. Intriguingly, the local packing density around both hot spots and conserved residues is higher than expected. We further observe a correlation between local packing density and experimental deltadeltaG. Favorable conserved pairs include Gly coupled with aromatics, charged and polar residues, as well as aromatic residue coupling. Remarkably, charged residue couples are underrepresented. Overall, protein-protein interactions appear to consist of regions of high and low packing density, with the hot spots organized in the former. The high local packing density in binding interfaces is reminiscent of protein cores.
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Inbal
I
Halperin
Haim
H
Wolfson
Ruth
R
Nussinov
D000409:Alanine / Q000737:chemistry; D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019992:Databases as Topic; D005998:Glycine / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D005810:Multigene Family; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
D000596:Amino Acids; D006023:Glycoproteins; D000409:Alanine; D005998:Glycine