The jigsaw puzzle model: search for conformational specificity in protein interiors.
The jigsaw puzzle model postulates that the predominant factor relating primary sequence to three-dimensional fold lies in the stereospecific packing of interdigitating side-chains within densely packed protein interiors. An attempt has been made to check the validity of the model by means of a surface complementarity function. Out of a database of 100 highly resolved protein structures the contacts between buried hydrophobic residues (Leu, Ile, Val, Phe) and their neighbours have been categorized in terms of the extent of side-chain surface area involved in a contact (overlap) and their steric fit (Sm). The results show that the majority of contacts between a buried residue and its immediate neighbours (side-chains) are of high steric fit and in the case of extended overlap at least one of the angular parameters characterizing interresidue geometry to have pronounced deviation from a random distribution, estimated by chi(2). The calculations thus tend to support the "jigsaw puzzle" model in that 75-85% of the contacts involving hydrophobic residues are of high surface complementarity, which, coupled to high overlap, exercise fairly stringent constraints over the possible geometrical orientations between interacting residues. These constraints manifest in simple patterns in the distributions of orientational angles. Approximately 60-80% of the buried side-chain surface packs against neighbouring side-chains, the rest interacting with main-chain atoms. The latter partition of the surface maintains an equally high steric fit (relative to side-chain contacts) emphasizing a non-trivial though secondary role played by main-chain atoms in interior packing. The majority of this class of contacts, though of high complementarity, is of reduced overlap. All residues whether hydrophobic or polar/charged show similar surface complementarity measures upon burial, indicating comparable competence of all amino acids in packing effectively with their atomic environments. The specificity thus appears to be distributed over the entire network of contacts within proteins. The study concludes with a proposal to classify contacts as specific and non-specific (based on overlap and fit), with the former perhaps contributing more to the specificity between sequence and fold than the latter.
D000596:Amino Acids / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*
D000596:Amino Acids; D011506:Proteins