title: Conformational dynamics of a membrane protein chaperone enables spatially regulated substrate capture and release.
abstract: 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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;
authors.forename: Fu-Cheng
authors.initials: FC
authors.lastname: Liang
authors.affiliation: Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Gerard
authors.initials: G
authors.lastname: Kroon
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;
authors.forename: Camille Z
authors.initials: CZ
authors.lastname: McAvoy
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;
authors.forename: Chris
authors.initials: C
authors.lastname: Chi
authors.affiliation: Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037 wright@scripps.edu sshan@caltech.edu.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Wright
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125; wright@scripps.edu sshan@caltech.edu.
authors.forename: Shu-Ou
authors.initials: SO
authors.lastname: Shan
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D060365:Chloroplast Proteins / Q000737:chemistry* / Q000378:metabolism; D045342:Light-Harvesting Protein Complexes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship; D060431:Thylakoid Membrane Proteins / Q000378:metabolism; D020524:Thylakoids / Q000378:metabolism
chemical_list: C106404:ALBINO 3 protein, Arabidopsis; D029681:Arabidopsis Proteins; D060365:Chloroplast Proteins; D045342:Light-Harvesting Protein Complexes; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D018271:Signal Recognition Particle; D060431:Thylakoid Membrane Proteins; C568473:cpSRP43 protein, Arabidopsis
keywords: NMR spectroscopy; membrane protein biogenesis; molecular chaperone; protein dynamics; signal recognition particle