A FUNCTIONAL-ROLE FOR PROTEIN CAVITIES IN DOMAIN-DOMAIN MOTIONS

Motions between individual domains are known to play an important role in protein function. Protein cavities at domain interfaces have been suggested to facilitate such movements. Consequently, the cavity morph ology in a set of multi-domain proteins has been critically examined. The conformational changes were well characterised by atomic resolutio n tertiary structures prior to and after domain motions. The results s howed that interdomain cavities play a number of specific functional r oles by either facilitating, or being otherwise involved with, domain: domain motions. Correspondingly, a higher fraction of cavity surface i s observed at domain interfaces as compared to that buried within indi vidual domains. Furthermore, interdomain cavity-forming residues were found to be highly conserved in terms of amino acid residue sequence a nd volume within their aligned protein families, more so than residues exclusive to the domain interface and intradomain cavities. These res ults provide substantial evidence of cavities fulfilling a specific fu nctional role in multi-domain proteins. (C) 1996 Academic Press Limite d