ArticleJournal of molecular biology2011
The four hydrophobic residues on the Hsp70 inter-domain linker have two distinct roles.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- TheFrontiers in molecular biosciences · 2023Review
- Conformational dynamics of the Hsp70 chaperone throughout key steps of its ATPase cycle.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A novel and unique ATP hydrolysis to AMP by a human Hsp70 Binding immunoglobin protein (BiP).Protein science : a publication of the Protein Society · 2022Article
- Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD.Nature communications · 2021Article
- Exported plasmodial J domain protein, PFE0055c, and PfHsp70-x form a specific co-chaperone-chaperone partnership.Cell stress & chaperones · 2021Article
- The Hsp70-Chaperone Machines in Bacteria.Frontiers in molecular biosciences · 2021Review
- Structural and functional analysis of the Hsp70/Hsp40 chaperone system.Protein science : a publication of the Protein Society · 2020Review
- An unexpected second binding site for polypeptide substrates is essential for Hsp70 chaperone activity.The Journal of biological chemistry · 2020Article
- Review
- Mitotic phosphorylation regulates Hsp72 spindle localization by uncoupling ATP binding from substrate release.Science signaling · 2018Article
- Intra-molecular pathways of allosteric control in Hsp70s.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- (-)-Epigallocatechin-3-Gallate Inhibits the Chaperone Activity of Plasmodium falciparum Hsp70 Chaperones and Abrogates Their Association with Functional Partners.Molecules (Basel, Switzerland) · 2017Article
- Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s.Nature communications · 2017Article
- AMPylation targets the rate-limiting step of BiP's ATPase cycle for its functional inactivation.eLife · 2017Article
- Hsp70's RNA-binding and mRNA-stabilizing activities are independent of its protein chaperone functions.The Journal of biological chemistry · 2017Article
- A disulfide-bonded DnaK dimer is maintained in an ATP-bound state.Cell stress & chaperones · 2017Article
- Close and Allosteric Opening of the Polypeptide-Binding Site in a Human Hsp70 Chaperone BiP.Structure (London, England : 1993) · 2015Article
- Physiological modulation of BiP activity by trans-protomer engagement of the interdomain linker.eLife · 2015Article
- Pathways of allosteric regulation in Hsp70 chaperones.Nature communications · 2015Article
- Substrate-binding domain conformational dynamics mediate Hsp70 allostery.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The ubiquitous molecular chaperone 70-kDa heat shock proteins (Hsp70) play key roles in maintaining protein homeostasis. Hsp70s contain two functional domains: a nucleotide binding domain and a substrate binding domain. The two domains are connected by a highly conserved inter-domain linker, and allosteric coupling between the two domains is critical for chaperone function. The auxiliary chaperone 40-kDa heat shock proteins (Hsp40) facilitate all the biological processes associated with Hsp70s by stimulating the ATPase activity of Hsp70s. Although an overall essential role of the inter-domain linker in both allosteric coupling and Hsp40 interaction has been suggested, the molecular mechanisms remain largely unknown. Previously, we reported a crystal structure of a full-length Hsp70 homolog, in which the inter-domain linker forms a well-ordered β strand. Four highly conserved hydrophobic residues reside on the inter-domain linker. In DnaK, a well-studied Hsp70, these residues are V389, L390, L391, and L392. In this study, we biochemically dissected their roles. The inward-facing side chains of V389 and L391 form extensive hydrophobic contacts with the nucleotide binding domain, suggesting their essential roles in coupling the two functional domains, a hypothesis confirmed by mutational analysis. On the other hand, L390 and L392 face outward on the surface. Mutation of either abolishes DnaK's in vivo function, yet intrinsic biochemical properties remain largely intact. In contrast, Hsp40 interaction is severely compromised. Thus, for the first time, we separated the two essential roles of the highly conserved Hsp70 inter-domain linker: coupling the two functional domains through V389 and L391 and mediating the interaction with Hsp40 through L390 and L392.
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