Hsp110 nucleotide exchange factors may amplify Hsp70-disaggregation by enhanced entropic pulling.
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| Title: | Hsp110 nucleotide exchange factors may amplify Hsp70-disaggregation by enhanced entropic pulling. |
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| Authors: | Rebeaud, Mathieu E.1,2, Fauvet, Bruno1,3, De Los Rios, Paolo1,3 paolo.delosrios@epfl.ch, Goloubinoff, Pierre2 pierre.goloubinoff@unil.ch |
| Source: | Journal of Biological Chemistry. Aug2025, Vol. 301 Issue 8, p1-14. 14p. |
| Subjects: | Heat shock proteins, Nucleotide exchange factors, Protein fractionation, Molecular chaperones, Catalysts |
| Abstract: | Hsp70s use energy from ATP hydrolysis to unfold protein structures and solubilize stable aggregates and accumulate native species, even under adverse non-native conditions. To carry out its catalytic polypeptide-unfolding activity, Hsp70 needs to reversibly interact with a J-domain (JDP) catalyst, a misfolded or alternatively-folded polypeptide substrate and a nucleotide exchange factor (NEF), which binds to the nucleotide-binding domain (NBD), accelerates ADP-release, and controls the dissociation of the unfolded polypeptide product of the unfolding reaction. In bacteria, GrpE is the ubiquitous NEF, and yet, during the process of eukaryotization, it was lost from the cytosol, to be replaced by novel NEF proteins, among which the Hsp110 family stands out. Curiously, Hsp110s belong to the Hsp70 superfamily, but the evolutionary steps that led from an ancestral Hsp70 unfoldase to a Hsp110 NEF catalyzing other Hsp70's activity remain unsolved. Combining experiments using wild-type Sse1 (yeast Hsp110) and rationally designed mutants, we show that Hsp110 is likely built upon some distinctive features already present in Hsp70 by repurposing them, rather than by fashioning novel molecular properties. Taking all results together, we suggest a novel mechanism of action of Hsp110, whereby it is a NEF that also enhances the unfolding/disaggregating entropic pulling forces generated by Hsp70, by transiently increasing the chaperone's effective volume. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 187735753 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Hsp110 nucleotide exchange factors may amplify Hsp70-disaggregation by enhanced entropic pulling. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Rebeaud%2C+Mathieu+E%2E%22">Rebeaud, Mathieu E.</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Fauvet%2C+Bruno%22">Fauvet, Bruno</searchLink><relatesTo>1,3</relatesTo><br /><searchLink fieldCode="AR" term="%22De+Los+Rios%2C+Paolo%22">De Los Rios, Paolo</searchLink><relatesTo>1,3</relatesTo><i> paolo.delosrios@epfl.ch</i><br /><searchLink fieldCode="AR" term="%22Goloubinoff%2C+Pierre%22">Goloubinoff, Pierre</searchLink><relatesTo>2</relatesTo><i> pierre.goloubinoff@unil.ch</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. Aug2025, Vol. 301 Issue 8, p1-14. 14p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Heat+shock+proteins%22">Heat shock proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleotide+exchange+factors%22">Nucleotide exchange factors</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+fractionation%22">Protein fractionation</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+chaperones%22">Molecular chaperones</searchLink><br /><searchLink fieldCode="DE" term="%22Catalysts%22">Catalysts</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Hsp70s use energy from ATP hydrolysis to unfold protein structures and solubilize stable aggregates and accumulate native species, even under adverse non-native conditions. To carry out its catalytic polypeptide-unfolding activity, Hsp70 needs to reversibly interact with a J-domain (JDP) catalyst, a misfolded or alternatively-folded polypeptide substrate and a nucleotide exchange factor (NEF), which binds to the nucleotide-binding domain (NBD), accelerates ADP-release, and controls the dissociation of the unfolded polypeptide product of the unfolding reaction. In bacteria, GrpE is the ubiquitous NEF, and yet, during the process of eukaryotization, it was lost from the cytosol, to be replaced by novel NEF proteins, among which the Hsp110 family stands out. Curiously, Hsp110s belong to the Hsp70 superfamily, but the evolutionary steps that led from an ancestral Hsp70 unfoldase to a Hsp110 NEF catalyzing other Hsp70's activity remain unsolved. Combining experiments using wild-type Sse1 (yeast Hsp110) and rationally designed mutants, we show that Hsp110 is likely built upon some distinctive features already present in Hsp70 by repurposing them, rather than by fashioning novel molecular properties. Taking all results together, we suggest a novel mechanism of action of Hsp110, whereby it is a NEF that also enhances the unfolding/disaggregating entropic pulling forces generated by Hsp70, by transiently increasing the chaperone's effective volume. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.jbc.2025.110450 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 14 StartPage: 1 Subjects: – SubjectFull: Heat shock proteins Type: general – SubjectFull: Nucleotide exchange factors Type: general – SubjectFull: Protein fractionation Type: general – SubjectFull: Molecular chaperones Type: general – SubjectFull: Catalysts Type: general Titles: – TitleFull: Hsp110 nucleotide exchange factors may amplify Hsp70-disaggregation by enhanced entropic pulling. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Rebeaud, Mathieu E. – PersonEntity: Name: NameFull: Fauvet, Bruno – PersonEntity: Name: NameFull: De Los Rios, Paolo – PersonEntity: Name: NameFull: Goloubinoff, Pierre IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 08 Text: Aug2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 301 – Type: issue Value: 8 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
