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

Georg K.A. Hochberg, Dale A. Shepherd, Erik G. Marklund, Indu Santhanagoplan, Matteo T. Degiacomi, Arthur Laganowsky, Timothy M. Allison, Eman Basha, Michael T. Marty, Martin R. Galpin, Weston B. Struwe, Andrew J. Baldwin, Elizabeth Vierling, Justin L.P. Benesch

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)930-935
Number of pages6
JournalScience
Volume359
Issue number6378
DOIs
StatePublished - Feb 23 2018
Externally publishedYes

ASJC Scopus subject areas

  • General

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