Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions.

Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions.
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DOI:
10.1126/science.aam7229
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发表时间:
2018-02-23
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Benesch JLP
Benesch JLP
中科院分区:
其他
文献类型:
--
作者:
Hochberg GKA;Shepherd DA;Marklund EG;Santhanagoplan I;Degiacomi MT;Laganowsky A;Allison TM;Basha E;Marty MT;Galpin MR;Struwe WB;Baldwin AJ;Vierling E;Benesch JLP

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Oligomeric proteins assemble with remarkable selectivity, even in the presence of closely related proteins, in order 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 co-assembly 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 oligomerisation. Conformational flexibility at non-interfacial regions in the monomers prevents co-assembly, allowing interfaces to remain largely conserved. Homomeric oligomers must overcome the entropic benefit of co-assembly and, accordingly, homomeric paralogs comprise fewer subunits than homomers that have no paralogs. Small heat-shock proteins avoid dysfunctional co-assembly using mechanisms that cause minimal disruption to their conserved interfaces
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