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Published March 22, 2016 | Published + Supplemental Material
Journal Article Open

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


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.

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 www.pnas.org/lookup/suppl/doi:10.1073/pnas.1524777113/-/DCSupplemental.

Attached Files

Published - PNAS-2016-Liang-E1615-24.pdf

Supplemental Material - pnas.201524777SI.pdf


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