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