Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions
AuthorHochberg, Georg K. A.
Shepherd, Dale A.
Marklund, Erik G.
Degiacomi, Matteo T.
Allison, Timothy M.
Marty, Michael T.
Galpin, Martin R.
Struwe, Weston B.
Baldwin, Andrew J.
Benesch, Justin L. P.
AffiliationUniv Arizona, Dept Chem & Biochem
MetadataShow full item record
PublisherAMER ASSOC ADVANCEMENT SCIENCE
CitationHochberg, G. K., Shepherd, D. A., Marklund, E. G., Santhanagoplan, I., Degiacomi, M. T., Laganowsky, A., ... & Struwe, W. B. (2018). Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions. Science, 359(6378), 930-935.
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AbstractOligomeric 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.
VersionFinal accepted manuscript
SponsorsEngineering and Physical Sciences Research Council [EP/J01835X/1]; Carl Trygger's Foundation; Swiss National Science Foundation [P2ELP3_155339]; Biotechnology and Biological Sciences Research Council [BB/J014346/1, BB/K004247/1, BB/J018082/1]; National Institutes of Health [RO1 GM42761]; Massachusetts Life Sciences Center; Royal Society