title: Protein unfolding as a switch from self-recognition to high-affinity client binding.
abstract: Stress-specific activation of the chaperone Hsp33 requires the unfolding of a central linker region. This activation mechanism suggests an intriguing functional relationship between the chaperone's own partial unfolding and its ability to bind other partially folded client proteins. However, identifying where Hsp33 binds its clients has remained a major gap in our understanding of Hsp33's working mechanism. By using site-specific Fluorine-19 nuclear magnetic resonance experiments guided by in vivo crosslinking studies, we now reveal that the partial unfolding of Hsp33's linker region facilitates client binding to an amphipathic docking surface on Hsp33. Furthermore, our results provide experimental evidence for the direct involvement of conditionally disordered regions in unfolded protein binding. The observed structural similarities between Hsp33's own metastable linker region and client proteins present a possible model for how Hsp33 uses protein unfolding as a switch from self-recognition to high-affinity client binding.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N-University Avenue, Ann Arbor, Michigan 48109-1048, USA.
authors.forename: Bastian
authors.initials: B
authors.lastname: Groitl
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N-University Avenue, Ann Arbor, Michigan 48109-1048, USA.|Howard Hughes Medical Institute, University of Michigan, 830 N-University Avenue, Ann Arbor, Michigan 48109-1048, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Horowitz
authors.affiliation: Department of Biochemistry and Microbiology, Genome BC Proteomics Centre, University of Victoria, 4464 Markham Street #3101, Victoria, British Columbia, Canada V8Z5N3.
authors.forename: Karl A T
authors.initials: KAT
authors.lastname: Makepeace
authors.affiliation: Department of Biochemistry and Microbiology, Genome BC Proteomics Centre, University of Victoria, 4464 Markham Street #3101, Victoria, British Columbia, Canada V8Z5N3.
authors.forename: Evgeniy V
authors.initials: EV
authors.lastname: Petrotchenko
authors.affiliation: Department of Biochemistry and Microbiology, Genome BC Proteomics Centre, University of Victoria, 4464 Markham Street #3101, Victoria, British Columbia, Canada V8Z5N3.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N-University Avenue, Ann Arbor, Michigan 48109-1048, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Reichmann
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N-University Avenue, Ann Arbor, Michigan 48109-1048, USA.|Howard Hughes Medical Institute, University of Michigan, 830 N-University Avenue, Ann Arbor, Michigan 48109-1048, USA.
authors.forename: James C A
authors.initials: JCA
authors.lastname: Bardwell
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N-University Avenue, Ann Arbor, Michigan 48109-1048, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Jakob
mesh_terms: D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D066235:Fluorine-19 Magnetic Resonance Imaging / Q000379:methods*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding
chemical_list: D029968:Escherichia coli Proteins; C492165:HSP33 protein, E coli; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010455:Peptides