Identifying Structural Domains in Proteins

Abstract

Analysisofproteinstructurestypicallybeginswithdecompositionofthestructureintomorebasic units called structural domains. The underlying goal is to reduce a complex proteinstructuretoasetofsimpler,yetstructurallymeaningfulunits,eachofwhichcanbeanalyzedindependently. Structural semi-independence of domains is their hallmark: domains oftenhave compact structure that can fold (and sometimes function) independently. The totalnumber of distinct structural domains is currently hovering around one thousand: they arerepresented by the unique folds in SCOP classification (Murzin et al., 1995) or uniquetopologies in CATH classification (Orengo et al., 1997). Interestingly, this is what Chothiapredicted at a rather early stage of the Structural Genomics era (Chothia, 1992).Asignificantfractionofthesedomainsisuniversaltoalllifeforms,othersarekingdom-specificandyetothersareconfinedtosubgroupsofspecies(PontingandRussell,2002;Yang,and Doolittle, and Bourne, 2005). The enormous variety of protein structures is thenachievedthroughcombinationofvariousdomainswithinasinglestructure.This‘‘combin-ing’’ofdomainscan be achievedbycombiningtogether single domainpolypeptide chainswithin a noncovalently linked structure or by combining domains (via gene fusions/recombination) on a single polypeptide chain that folds into the final structure (Bennett,Choe,andEisenberg,1994).Therearebenefitstobothstrategies:theformercanbeseenasamoreeconomicandmodularapproachinwhichmanydifferentstructurescanbeputtogetherwith relatively few components within the cell. The latter, combining a specific set ofmodules within a single polypeptide chain, ensures that they are expressed together andlocalized in the same cells or cellular compartments (Tsoka and Ouzounis, 2000). Thischapterisconcernedwiththislattercase:thedecompositionofthemultidomainpolypeptidechain into structural domains.