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

doi:10.1126/science.aam7229

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

Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

49 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 language	English (US)
Pages (from-to)	930-935
Number of pages	6
Journal	Science
Volume	359
Issue number	6378
DOIs	https://doi.org/10.1126/science.aam7229
State	Published - Feb 23 2018

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10.1126/science.aam7229

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Hochberg, G. K. A., Shepherd, D. A., Marklund, E. G., Santhanagoplan, I., Degiacomi, M. T., Laganowsky, A., Allison, T. M., Basha, E., Marty, M. T., Galpin, M. R., Struwe, W. B., Baldwin, A. J., Vierling, E., & Benesch, J. 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

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 2018, 'Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions', Science, vol. 359, no. 6378, pp. 930-935. https://doi.org/10.1126/science.aam7229

@article{3344608288264e41bf2d74551b4d6716,

title = "Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions",

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.",

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

note = "Funding Information: We thank C. Robinson, J. Schnell, P. Kukura, D. Staunton (all at University of Oxford), and B. Metzger (University of Chicago) for helpful discussions. We acknowledge access to B21 and help from M. Tully and J. Doutch at the Diamond Synchrotron (J.L.P.B. for SM9384-2); and the ARCUS cluster at Advanced Research Computing, Oxford. We thank the following funding sources: Engineering and Physical Sciences Research Council (G.K.A.H. for a studentship, J.L.P.B. for EP/J01835X/1); Carl Trygger's Foundation (E.G.M.); Swiss National Science Foundation (M.T.D. for P2ELP3-155339) and Biotechnology and Biological Sciences Research Council (A.J.B. for BB/J014346/1, J.L.P.B. for BB/K004247/1 and BB/J018082/1); National Institutes of Health (E.V. for RO1 GM42761); Massachusetts Life Sciences Center (E.V. for a New Faculty Research Award); and the Royal Society (J.L.P.B. for a University Research Fellowship). All data necessary to support the conclusions are available in the manuscript or supplementary materials and are deposited with DOI 10.5287/bodleian:54jBVeAzw. Funding Information: We thank C. Robinson, J. Schnell, P. Kukura, D. Staunton (all at University of Oxford), and B. Metzger (University of Chicago) for helpful discussions. We acknowledge access to B21 and help from M. Tully and J. Doutch at the Diamond Synchrotron (J.L.P.B. for SM9384-2); and the ARCUS cluster at Advanced Research Computing, Oxford. We thank the following funding sources: Engineering and Physical Sciences Research Council (G.K.A.H. for a studentship, J.L.P.B. for EP/J01835X/1); Carl Trygger{\textquoteright}s Foundation (E.G.M.); Swiss National Science Foundation (M.T.D. for P2ELP3_155339) and Biotechnology and Biological Sciences Research Council (A.J.B. for BB/J014346/1, J.L.P.B. for BB/K004247/1 and BB/J018082/1); National Institutes of Health (E.V. for RO1 GM42761); Massachusetts Life Sciences Center (E.V. for a New Faculty Research Award); and the Royal Society (J.L.P.B. for a University Research Fellowship). All data necessary to support the conclusions are available in the manuscript or supplementary materials and are deposited with DOI 10.5287/bodleian:54jBVeAzw. Publisher Copyright: {\textcopyright} 2017 The Authors.",

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doi = "10.1126/science.aam7229",

language = "English (US)",

volume = "359",

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T1 - Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions

AU - Hochberg, Georg K.A.

AU - Shepherd, Dale A.

AU - Marklund, Erik G.

AU - Santhanagoplan, Indu

AU - Degiacomi, Matteo T.

AU - Laganowsky, Arthur

AU - Allison, Timothy M.

AU - Basha, Eman

AU - Marty, Michael T.

AU - Galpin, Martin R.

AU - Struwe, Weston B.

AU - Baldwin, Andrew J.

AU - Vierling, Elizabeth

AU - Benesch, Justin L.P.

N1 - Funding Information: We thank C. Robinson, J. Schnell, P. Kukura, D. Staunton (all at University of Oxford), and B. Metzger (University of Chicago) for helpful discussions. We acknowledge access to B21 and help from M. Tully and J. Doutch at the Diamond Synchrotron (J.L.P.B. for SM9384-2); and the ARCUS cluster at Advanced Research Computing, Oxford. We thank the following funding sources: Engineering and Physical Sciences Research Council (G.K.A.H. for a studentship, J.L.P.B. for EP/J01835X/1); Carl Trygger's Foundation (E.G.M.); Swiss National Science Foundation (M.T.D. for P2ELP3-155339) and Biotechnology and Biological Sciences Research Council (A.J.B. for BB/J014346/1, J.L.P.B. for BB/K004247/1 and BB/J018082/1); National Institutes of Health (E.V. for RO1 GM42761); Massachusetts Life Sciences Center (E.V. for a New Faculty Research Award); and the Royal Society (J.L.P.B. for a University Research Fellowship). All data necessary to support the conclusions are available in the manuscript or supplementary materials and are deposited with DOI 10.5287/bodleian:54jBVeAzw. Funding Information: We thank C. Robinson, J. Schnell, P. Kukura, D. Staunton (all at University of Oxford), and B. Metzger (University of Chicago) for helpful discussions. We acknowledge access to B21 and help from M. Tully and J. Doutch at the Diamond Synchrotron (J.L.P.B. for SM9384-2); and the ARCUS cluster at Advanced Research Computing, Oxford. We thank the following funding sources: Engineering and Physical Sciences Research Council (G.K.A.H. for a studentship, J.L.P.B. for EP/J01835X/1); Carl Trygger’s Foundation (E.G.M.); Swiss National Science Foundation (M.T.D. for P2ELP3_155339) and Biotechnology and Biological Sciences Research Council (A.J.B. for BB/J014346/1, J.L.P.B. for BB/K004247/1 and BB/J018082/1); National Institutes of Health (E.V. for RO1 GM42761); Massachusetts Life Sciences Center (E.V. for a New Faculty Research Award); and the Royal Society (J.L.P.B. for a University Research Fellowship). All data necessary to support the conclusions are available in the manuscript or supplementary materials and are deposited with DOI 10.5287/bodleian:54jBVeAzw. Publisher Copyright: © 2017 The Authors.

PY - 2018/2/23

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N2 - 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.

AB - 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.

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

Abstract

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Core domain of the class I small heat-shock protein HSP 18.1 from Pisum sativum

Core domain of the class II small heat-shock protein HSP 17.7 from Pisum sativum

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

Abstract

ASJC Scopus subject areas

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Other files and links

Fingerprint

Datasets

Core domain of the class I small heat-shock protein HSP 18.1 from Pisum sativum

Core domain of the class II small heat-shock protein HSP 17.7 from Pisum sativum

Cite this