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Conformational dynamics of a membrane protein chaperone enables spatially regulated substrate capture and release

Liang, Fu-Cheng and Kroon, Gerard and McAvoy, Camille Z. and Chi, Chris and Wright, Peter E. and Shan, Shu-ou (2016) Conformational dynamics of a membrane protein chaperone enables spatially regulated substrate capture and release. Proceedings of the National Academy of Sciences of the United States of America, 113 (12). E1615-E1624. ISSN 0027-8424. PMCID PMC4812700. doi:10.1073/pnas.1524777113.

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Membrane protein biogenesis poses enormous challenges to cellular protein homeostasis and requires effective molecular chaperones. Compared with chaperones that promote soluble protein folding, membrane protein chaperones require tight spatiotemporal coordination of their substrate binding and release cycles. Here we define the chaperone cycle for cpSRP43, which protects the largest family of membrane proteins, the light harvesting chlorophyll a/b-binding proteins (LHCPs), during their delivery. Biochemical and NMR analyses demonstrate that cpSRP43 samples three distinct conformations. The stromal factor cpSRP54 drives cpSRP43 to the active state, allowing it to tightly bind substrate in the aqueous compartment. Bidentate interactions with the Alb3 translocase drive cpSRP43 to a partially inactive state, triggering selective release of LHCP’s transmembrane domains in a productive unloading complex at the membrane. Our work demonstrates how the intrinsic conformational dynamics of a chaperone enables spatially coordinated substrate capture and release, which may be general to other ATP-independent chaperone systems.

Item Type:Article
Related URLs:
URLURL TypeDescription Information CentralArticle
Kroon, Gerard0000-0001-8038-7476
Wright, Peter E.0000-0002-1368-0223
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2016 National Academy of Sciences. Edited by Gerhard Wagner, Harvard Medical School, Boston, MA, and approved February 4, 2016 (received for review December 16, 2015). Published online before print March 7, 2016. We thank R. Dalbey and P. Jaru-Ampornpan for plasmid encoding Alb3CT, V. Q. Lam and M. Yamout for initial optimization of the isotope labeling condition, P. Aoto for advice on NMR assignments, S. Chandrasekar and S. Lieblich (S. Mayo’s laboratory) for help with analytical ultracentrifugation, and members of the S.-o.S. laboratory for comments on the manuscript. This work was supported by fellowships from the Gordon and Betty Moore Foundation and American Federation for Aging Research. (to S.-o.S.) and the Skaggs Institute of Chemical Biology (to P.E.W.). Author contributions: F.-C.L., G.K., C.Z.M., P.E.W., and S.-o.S. designed research; F.-C.L., G.K., and C.Z.M. performed research; F.-C.L., G.K., C.Z.M., C.C., P.E.W., and S.-o.S. analyzed data; and F.-C.L., P.E.W., and S.-o.S. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. This article contains supporting information online at
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
American Federation for Aging ResearchUNSPECIFIED
Skaggs Institute of Chemical BiologyUNSPECIFIED
Subject Keywords:membrane protein biogenesis; molecular chaperone; signal recognition particle; protein dynamics; NMR spectroscopy
Issue or Number:12
PubMed Central ID:PMC4812700
Record Number:CaltechAUTHORS:20160308-073550753
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Official Citation:Fu-Cheng Liang, Gerard Kroon, Camille Z. McAvoy, Chris Chi, Peter E. Wright, and Shu-ou Shan Conformational dynamics of a membrane protein chaperone enables spatially regulated substrate capture and release PNAS 2016 113 (12) E1615-E1624; published ahead of print March 7, 2016, doi:10.1073/pnas.1524777113
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65172
Deposited By: Tony Diaz
Deposited On:08 Mar 2016 15:46
Last Modified:06 May 2022 16:34

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