Hochberg Georg K A, Shepherd Dale A, Marklund Erik G, Santhanagoplan Indu, Degiacomi Matteo T, Laganowsky Arthur, Allison Timothy M, Basha Eman, Marty Michael T, Galpin Martin R, Struwe Weston B, Baldwin Andrew J, Vierling Elizabeth, Benesch Justin L P
Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3QZ, UK.
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA.
Science. 2018 Feb 23;359(6378):930-935. doi: 10.1126/science.aam7229.
Oligomeric proteins assemble with exceptional selectivity, even in the presence of closely related proteins, to perform their cellular roles. We show that most proteins related by gene duplication of an oligomeric ancestor have evolved to avoid hetero-oligomerization and that this correlates with their acquisition of distinct functions. We report how coassembly is avoided by two oligomeric small heat-shock protein paralogs. A hierarchy of assembly, involving intermediates that are populated only fleetingly at equilibrium, ensures selective oligomerization. Conformational flexibility at noninterfacial regions in the monomers prevents coassembly, allowing interfaces to remain largely conserved. Homomeric oligomers must overcome the entropic benefit of coassembly and, accordingly, homomeric paralogs comprise fewer subunits than homomers that have no paralogs.
寡聚蛋白即使在存在密切相关蛋白质的情况下，也能以极高的选择性组装，以履行其细胞功能。我们表明，大多数由寡聚祖先基因复制产生的相关蛋白质已经进化到避免异源寡聚化，并且这与它们获得不同功能相关。我们报告了两个寡聚小热休克蛋白旁系同源物是如何避免共组装的。一种组装层次结构，涉及在平衡时仅短暂存在的中间体，确保了选择性寡聚化。单体中非界面区域的构象灵活性阻止了共组装，使界面在很大程度上得以保留。同源寡聚体必须克服共组装的熵增优势，因此，同源旁系同源物包含的亚基比没有旁系同源物的同源物少。
