Ligand Binding Site Structure Shapes Folding, Assembly and Degradation of Homomeric Protein Complexes.
Ligand binding site structure has profound consequences for the evolution of function of protein complexes, particularly in homomers-complexes comprising multiple copies of the same protein. Previously, we have shown that homomers with multichain binding sites (MBSs) are characterized by more conserved binding sites and quaternary structure, and qualitatively different allosteric pathways than homomers with single-chain binding sites (SBSs) or monomers. Here, using computational methods, we show that the folds of single-domain MBS and SBS homomers are different, and SBS homomers are likely to be folded cotranslationally, while MBS homomers are more likely to form post-translationally and rely on more advanced folding-assistance and quality control mechanisms, which include chaperonins. In addition, our findings demonstrate that MBS homomers are qualitatively different from monomers, while SBS homomers are much less distinct, supporting the hypothesis that the evolution of quaternary structure in SBS homomers is significantly influenced by stochastic processes.
['Abrusán|György|G|', 'Marsh|Joseph A|JA|']
D000595:Amino Acid Sequence D001665:Binding Sites D017124:Conserved Sequence D004220:Disulfides D063990:Gene Ontology D006801:Humans D008024:Ligands D008958:Models, Molecular D018832:Molecular Chaperones D046912:Multiprotein Complexes D011485:Protein Binding D000072417:Protein Domains D017510:Protein Folding D025941:Protein Interaction Mapping D059748:Proteolysis D000074084:THP-1 Cells
ligand binding quaternary structure chaperones complex assembly protein folding