TY - JOUR
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
Y1 - 2018/2/23
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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U2 - 10.1126/science.aam7229
DO - 10.1126/science.aam7229
M3 - Article
C2 - 29472485
AN - SCOPUS:85042305989
SN - 0036-8075
VL - 359
SP - 930
EP - 935
JO - Science
JF - Science
IS - 6378
ER -