Protein unfolding as a switch from self-recognition to high-affinity client binding

Nature Communications
Bastian GroitlUrsula Jakob

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.

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Citations

Oct 4, 2016·Database : the Journal of Biological Databases and Curation·Nadav BrandesMichal Linial
Apr 27, 2018·Protein Science : a Publication of the Protein Society·Nathalie Casanova-MoralesChristian A M Wilson
Apr 18, 2018·Nature Communications·Daniel Andreas RutzJohannes Buchner
Mar 8, 2019·Nature Communications·T Reid AldersonAndrew J Baldwin
Aug 28, 2020·Frontiers in Microbiology·Samar AraminDana Reichmann
Oct 28, 2019·Nature Communications·Kevin WuJames C A Bardwell
Feb 10, 2019·Nature Communications·Filipa TeixeiraUrsula Jakob
Oct 5, 2019·F1000Research·Camille V Goemans, Jean-François Collet
Sep 30, 2020·Biological Chemistry·Kathrin UlrichUrsula Jakob
Nov 24, 2019·Biophysical Journal·Fatemeh MoayedSander J Tans
Nov 15, 2020·The Journal of Chemical Physics·Anna S KamenikKlaus R Liedl
Oct 17, 2017·Current Opinion in Structural Biology·Caitlin M DavisShahar Sukenik
Apr 4, 2021·Biomolecules·Meytal RadzinskiDana Reichmann
May 22, 2021·Frontiers in Molecular Biosciences·Emile Dupuy, Jean-François Collet

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Methods Mentioned

BETA
nuclear magnetic resonance
crosslinking studies
NMR
protein folding
electrophoresis
light scattering

Software Mentioned

DOCK
UCSF Chimera
TASSER
DXMSMS
Proteome Discoverer
Xcalibur
Gaussian
Gaussview

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