Conformational Selection in Substrate Recognition by Hsp70 Chaperones

Hsp70s are molecular chaperones involved in the folding and assembly of proteins. They recognize hydrophobic amino acid stretches in their substrate binding groove. However, a detailed understanding of substrate specificity is still missing. Here, we use the endoplasmic reticulum-resident Hsp70 BiP...

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Bibliographic Details
Published in:Journal of molecular biology 2013-02, Vol.425 (3), p.466-474
Main Authors: Marcinowski, Moritz, Rosam, Mathias, Seitz, Christine, Elferich, Johannes, Behnke, Julia, Bello, Claudia, Feige, Matthias J., Becker, Christian F.W., Antes, Iris, Buchner, Johannes
Format: Article
Language:English
Subjects:
amino acids
antibody
binding sites
BiP
Escherichia coli - chemistry
Escherichia coli - metabolism
Escherichia coli Proteins - chemistry
Escherichia coli Proteins - metabolism
Hsp70
HSP70 Heat-Shock Proteins - chemistry
HSP70 Heat-Shock Proteins - metabolism
hydrophobicity
Kinetics
Models, Molecular
molecular chaperone
molecular chaperones
Molecular Chaperones - chemistry
Molecular Chaperones - metabolism
Protein Binding
substrate conformation
Substrate Specificity
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Summary:Hsp70s are molecular chaperones involved in the folding and assembly of proteins. They recognize hydrophobic amino acid stretches in their substrate binding groove. However, a detailed understanding of substrate specificity is still missing. Here, we use the endoplasmic reticulum-resident Hsp70 BiP to identify binding sites in a natural client protein. Two sites are mutually recognized and form stable Hsp70–substrate complexes. In silico and in vitro analyses revealed an extended substrate conformation as a crucial factor for interaction and show an unexpected plasticity of the substrate binding groove. The basic binding mechanism is conserved among different Hsp70s. [Display omitted] ► Structural aspects of Hsp70 substrate binding are still poorly understood. ► BiP binding sites in an authentic client protein have been identified. ► Substrate conformation is a critical factor for Hsp70 binding.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2012.11.030