Ligand Binding Site Structure Shapes Folding, Assembly and Degradation of Homomeric Protein Complexes

JOURNAL OF MOLECULAR BIOLOGY

卷:431

Article

Abrusan, Gyorgy¹  Marsh, Joseph A.¹ 

[1] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland

关键词: quaternary structure;    ligand binding;    protein folding;    complex assembly;    chaperones;   

DOI  :  10.1016/j.jmb.2019.07.014

来源: Elsevier

【 摘 要 】

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. (C) 2019 The Author(s). Published by Elsevier Ltd.

【 授权许可】

Free