title: A molecular mechanism of chaperone-client recognition.
abstract: Molecular chaperones are essential in aiding client proteins to fold into their native structure and in maintaining cellular protein homeostasis. However, mechanistic aspects of chaperone function are still not well understood at the atomic level. We use nuclear magnetic resonance spectroscopy to elucidate the mechanism underlying client recognition by the adenosine triphosphate-independent chaperone Spy at the atomic level and derive a structural model for the chaperone-client complex. Spy interacts with its partially folded client Im7 by selective recognition of flexible, locally frustrated regions in a dynamic fashion. The interaction with Spy destabilizes a partially folded client but spatially compacts an unfolded client conformational ensemble. By increasing client backbone dynamics, the chaperone facilitates the search for the native structure. A comparison of the interaction of Im7 with two other chaperones suggests that the underlying principle of recognizing frustrated segments is of a fundamental nature.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Lichun
authors.identifier: 0000-0002-0772-0452
authors.initials: L
authors.lastname: He
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Timothy
authors.initials: T
authors.lastname: Sharpe
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Adam
authors.initials: A
authors.lastname: Mazur
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Sebastian
authors.identifier: 0000-0002-6709-4684
authors.initials: S
authors.lastname: Hiller
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D018832:Molecular Chaperones / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D033903:Periplasmic Proteins / Q000737:chemistry*; D017510:Protein Folding
chemical_list: D002352:Carrier Proteins; C509253:E colicin-binding immunity protein Im7, E coli; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D033903:Periplasmic Proteins; C104888:Spy protein, E coli
keywords: Chaperone protein; Im7; NMR spectroscopy; protein dynamics; protein folding; protein-protein interaction; spy