Hochberg, Georg K. A. and Shepherd, Dale A. and Marklund, Erik G. and Santhanagoplan, Indu and Degiacomi, Matteo T. and Laganowsky, Arthur and Allison, Timothy M. and Basha, Eman and Marty, Michael T. and Galpin, Martin R. and Struwe, Weston B. and Baldwin, Andrew J. and Vierling, Elizabeth and Benesch, Justin L. P. (2018) 'Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions.', Science., 359 (6378). pp. 930-935.
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.
| Item Type: | Article |
|---|---|
| Full text: | (AM) Accepted Manuscript Download PDF (20323Kb) |
| Status: | Peer-reviewed |
| Publisher Web site: | https://doi.org/10.1126/science.aam7229 |
| Publisher 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 |
| Date accepted: | 08 January 2018 |
| Date deposited: | 27 February 2018 |
| Date of first online publication: | 23 February 2018 |
| Date first made open access: | 27 February 2018 |
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