Localization of protein-binding sites within families of proteins.
We address the question of whether or not the positions of protein-binding sites on homologous protein structures are conserved irrespective of the identities of their binding partners. First, for each domain family in the Structural Classification of Proteins (SCOP), protein-binding sites are extracted from our comprehensive database of structurally defined binary domain interactions (PIBASE). Second, the binding sites within each family are superposed using a structural alignment of its members. Finally, the degree of localization of binding sites within each family is quantified by comparing it with localization expected by chance. We found that 72% of the 1847 SCOP domain families in PIBASE have binding sites with localization values greater than expected by chance. Moreover, 554 (30%) of these families have localizations that are statistically significant (i.e., more than four standard deviations away from the mean expected by chance). In contrast, only 144 (8%) families have significantly low localization. The absence of a significant correlation of the binding site localization with the average sequence and structural conservations in a family suggests that localization can be helpful for describing the functional diversity of protein-protein interactions, complementing measures of sequence and structural conservation. Consideration of the binding site localization may also result in spatial restraints for the modeling of protein assembly structures.
Korkin
Dmitry
D
Department of Biopharmaceutical Sciences, University of California at San Francisco, San Francisco, CA 94143-2552, USA.
Davis
Fred P
FP
Sali
Andrej
A
D042964:Acyl-CoA Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D019143:Evolution, Molecular; D037181:Lectins, C-Type / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D037181:Lectins, C-Type; D011506:Proteins; D042964:Acyl-CoA Dehydrogenase