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A Disorder-to-Order Transition Activates an ATP-Independent Membrane Protein Chaperone

Siegel, Alex and McAvoy, Camille Z. and Lam, Vinh and Liang, Fu-Cheng and Kroon, Gerard and Miaou, Emily and Griffin, Patrick and Wright, Peter E. and Shan, Shu-ou (2020) A Disorder-to-Order Transition Activates an ATP-Independent Membrane Protein Chaperone. Journal of Molecular Biology, 432 (24). Art. No. 166708. ISSN 0022-2836. PMCID PMC7780713. doi:10.1016/j.jmb.2020.11.007.

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The 43 kDa subunit of the chloroplast signal recognition particle, cpSRP43, is an ATP-independent chaperone essential for the biogenesis of the light harvesting chlorophyll-binding proteins (LHCP), the most abundant membrane protein family on earth. cpSRP43 is activated by a stromal factor, cpSRP54, to more effectively capture and solubilize LHCPs. The molecular mechanism underlying this chaperone activation is unclear. Here, a combination of hydrogen–deuterium exchange, electron paramagnetic resonance, and NMR spectroscopy experiments reveal that a disorder-to-order transition of the ankyrin repeat motifs in the substrate binding domain of cpSRP43 drives its activation. An analogous coil-to-helix transition in the bridging helix, which connects the ankyrin repeat motifs to the cpSRP54 binding site in the second chromodomain, mediates long-range allosteric communication of cpSRP43 with its activating binding partner. Our results provide a molecular model to explain how the conformational dynamics of cpSRP43 enables regulation of its chaperone activity and suggest a general mechanism by which ATP-independent chaperones with cooperatively folding domains can be regulated.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Kroon, Gerard0000-0001-8038-7476
Griffin, Patrick0000-0002-3404-690X
Wright, Peter E.0000-0002-1368-0223
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2020 The Authors. Published by Elsevier Ltd.This is an open access article under the CC BY-NC-ND license ( Received 6 August 2020, Revised 5 November 2020, Accepted 6 November 2020, Available online 12 November 2020. We thank members of the Shan group for helpful comments on the manuscript and Dr. Peter Qin for helpful discussions in interpretation of the EPR data. This work was supported by NIH Training Grant 2T32 GM 7616-36 to Paul Sternberg, NIH R01 GM114390, NIH R35 GM136321, and DOE DE.SC0020661 to Shu-ou Shan, and the Skaggs Institute for Chemical Biology to Peter Wright. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CRediT authorship contribution statement: Alex Siegel: Conceptualization, Investigation, Formal analysis, Writing - original draft, Writing - review & editing. Camille Z. McAvoy: Conceptualization, Investigation, Formal analysis. Vinh Lam: Investigation, Formal analysis. Fu-Cheng Liang: Investigation, Formal analysis, Writing - original draft. Gerard Kroon: Methodology, Formal analysis. Emily Miaou: Investigation. Patrick Griffin: Methodology. Peter E. Wright: Supervision, Writing - review & editing. Shu-ou Shan: Supervision, Writing - review & editing.
Funding AgencyGrant Number
NIH Predoctoral Fellowship2T32 GM 7616-36
NIHR01 GM114390
NIHR35 GM136321
Department of Energy (DOE)DE-SC0020661
Skaggs Institute for Chemical BiologyUNSPECIFIED
Subject Keywords:chaperone; membrane protein biogenesis; protein dynamics; ankyrin repeat proteins; NMR spectroscopy
Issue or Number:24
PubMed Central ID:PMC7780713
Record Number:CaltechAUTHORS:20201113-100152867
Persistent URL:
Official Citation:Alex Siegel, Camille Z. McAvoy, Vinh Lam, Fu-Cheng Liang, Gerard Kroon, Emily Miaou, Patrick Griffin, Peter E. Wright, Shu-ou Shan, A Disorder-to-Order Transition Activates an ATP-Independent Membrane Protein Chaperone, Journal of Molecular Biology, Volume 432, Issue 24, 2020, 166708, ISSN 0022-2836,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106667
Deposited By: George Porter
Deposited On:16 Nov 2020 15:34
Last Modified:09 Feb 2022 23:57

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