Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces. / Seyffer, Fabian; Kummer, Eva; Oguchi, Yuki; Winkler, Juliane; Kumar, Mohit; Zahn, Regina; Sourjik, Victor; Bukau, Bernd; Mogk, Axel.

In: Nature Structural & Molecular Biology, Vol. 19, No. 12, 2012, p. 1347-55.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Seyffer, F, Kummer, E, Oguchi, Y, Winkler, J, Kumar, M, Zahn, R, Sourjik, V, Bukau, B & Mogk, A 2012, 'Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces', Nature Structural & Molecular Biology, vol. 19, no. 12, pp. 1347-55. https://doi.org/10.1038/nsmb.2442

APA

Seyffer, F., Kummer, E., Oguchi, Y., Winkler, J., Kumar, M., Zahn, R., Sourjik, V., Bukau, B., & Mogk, A. (2012). Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces. Nature Structural & Molecular Biology, 19(12), 1347-55. https://doi.org/10.1038/nsmb.2442

Vancouver

Seyffer F, Kummer E, Oguchi Y, Winkler J, Kumar M, Zahn R et al. Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces. Nature Structural & Molecular Biology. 2012;19(12):1347-55. https://doi.org/10.1038/nsmb.2442

Author

Seyffer, Fabian ; Kummer, Eva ; Oguchi, Yuki ; Winkler, Juliane ; Kumar, Mohit ; Zahn, Regina ; Sourjik, Victor ; Bukau, Bernd ; Mogk, Axel. / Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces. In: Nature Structural & Molecular Biology. 2012 ; Vol. 19, No. 12. pp. 1347-55.

Bibtex

@article{5b43ddc8e2984fe6baa5e0c9b8f1ad33,
title = "Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces",
abstract = "Bacteria, fungi and plants rescue aggregated proteins using a powerful bichaperone system composed of an Hsp70 chaperone and an Hsp100 AAA+ disaggregase. In Escherichia coli, the Hsp70 chaperone DnaK binds aggregates and targets the disaggregase ClpB to the substrate. ClpB hexamers use ATP to thread substrate polypeptides through the central pore, driving disaggregation. How ClpB finds DnaK and regulates threading remains unclear. To dissect the disaggregation mechanism, we separated these steps using primarily chimeric ClpB-ClpV constructs that directly recognize alternative substrates, thereby obviating DnaK involvement. We show that ClpB has low intrinsic disaggregation activity that is normally repressed by the ClpB middle (M) domain. In the presence of aggregate, DnaK directly binds M-domain motif 2, increasing ClpB ATPase activity to unleash high ClpB threading power. Our results uncover a new function for Hsp70: the coupling of substrate targeting to AAA+ chaperone activation at aggregate surfaces.",
keywords = "HSP70 Heat-Shock Proteins/metabolism, Protein Binding",
author = "Fabian Seyffer and Eva Kummer and Yuki Oguchi and Juliane Winkler and Mohit Kumar and Regina Zahn and Victor Sourjik and Bernd Bukau and Axel Mogk",
year = "2012",
doi = "10.1038/nsmb.2442",
language = "English",
volume = "19",
pages = "1347--55",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "nature publishing group",
number = "12",

}

RIS

TY - JOUR

T1 - Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces

AU - Seyffer, Fabian

AU - Kummer, Eva

AU - Oguchi, Yuki

AU - Winkler, Juliane

AU - Kumar, Mohit

AU - Zahn, Regina

AU - Sourjik, Victor

AU - Bukau, Bernd

AU - Mogk, Axel

PY - 2012

Y1 - 2012

N2 - Bacteria, fungi and plants rescue aggregated proteins using a powerful bichaperone system composed of an Hsp70 chaperone and an Hsp100 AAA+ disaggregase. In Escherichia coli, the Hsp70 chaperone DnaK binds aggregates and targets the disaggregase ClpB to the substrate. ClpB hexamers use ATP to thread substrate polypeptides through the central pore, driving disaggregation. How ClpB finds DnaK and regulates threading remains unclear. To dissect the disaggregation mechanism, we separated these steps using primarily chimeric ClpB-ClpV constructs that directly recognize alternative substrates, thereby obviating DnaK involvement. We show that ClpB has low intrinsic disaggregation activity that is normally repressed by the ClpB middle (M) domain. In the presence of aggregate, DnaK directly binds M-domain motif 2, increasing ClpB ATPase activity to unleash high ClpB threading power. Our results uncover a new function for Hsp70: the coupling of substrate targeting to AAA+ chaperone activation at aggregate surfaces.

AB - Bacteria, fungi and plants rescue aggregated proteins using a powerful bichaperone system composed of an Hsp70 chaperone and an Hsp100 AAA+ disaggregase. In Escherichia coli, the Hsp70 chaperone DnaK binds aggregates and targets the disaggregase ClpB to the substrate. ClpB hexamers use ATP to thread substrate polypeptides through the central pore, driving disaggregation. How ClpB finds DnaK and regulates threading remains unclear. To dissect the disaggregation mechanism, we separated these steps using primarily chimeric ClpB-ClpV constructs that directly recognize alternative substrates, thereby obviating DnaK involvement. We show that ClpB has low intrinsic disaggregation activity that is normally repressed by the ClpB middle (M) domain. In the presence of aggregate, DnaK directly binds M-domain motif 2, increasing ClpB ATPase activity to unleash high ClpB threading power. Our results uncover a new function for Hsp70: the coupling of substrate targeting to AAA+ chaperone activation at aggregate surfaces.

KW - HSP70 Heat-Shock Proteins/metabolism

KW - Protein Binding

U2 - 10.1038/nsmb.2442

DO - 10.1038/nsmb.2442

M3 - Journal article

C2 - 23160352

VL - 19

SP - 1347

EP - 1355

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 12

ER -

ID: 257865233