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

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.

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Authors

Georg K.A. Hochberg

Dale A. Shepherd

Erik G. Marklund

Indu Santhanagoplan

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



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.

Citation

Hochberg, G. K., Shepherd, D. A., Marklund, E. G., Santhanagoplan, I., Degiacomi, M. T., Laganowsky, A., …Benesch, J. L. (2018). Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions. Science, 359(6378), 930-935. https://doi.org/10.1126/science.aam7229

Journal Article Type Article
Acceptance Date Jan 8, 2018
Online Publication Date Feb 23, 2018
Publication Date Feb 23, 2018
Deposit Date Feb 26, 2018
Publicly Available Date Mar 29, 2024
Journal Science
Print ISSN 0036-8075
Electronic ISSN 1095-9203
Publisher American Association for the Advancement of Science
Peer Reviewed Peer Reviewed
Volume 359
Issue 6378
Pages 930-935
DOI https://doi.org/10.1126/science.aam7229

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Copyright Statement
This is the author’s version of the work. It is posted here by permission of the AAAS for personal
use, not for redistribution. The definitive version was published in 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. (2018). Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions. Science 359(6378): 930-935. https://doi.org/10.1126/science.aam7229





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