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

ABSTRACT: 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.

SUBMITTER: Siegel A

PROVIDER: S-EPMC7780713 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Siegel Alex A McAvoy Camille Z CZ Lam Vinh V Liang Fu-Cheng FC Kroon Gerard G Miaou Emily E Griffin Patrick P Wright Peter E PE Shan Shu-Ou SO

Journal of molecular biology 20201112 24

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 re ...[more]

PMID: 33188783

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

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

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