A tightly regulated molecular toggle controls AAA+ disaggregase

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

Standard

A tightly regulated molecular toggle controls AAA+ disaggregase. / Oguchi, Yuki; Kummer, Eva; Seyffer, Fabian; Berynskyy, Mykhaylo; Anstett, Benjamin; Zahn, Regina; Wade, Rebecca C; Mogk, Axel; Bukau, Bernd.

In: Nature Structural & Molecular Biology, Vol. 19, No. 12, 2012, p. 1338-46.

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

Harvard

Oguchi, Y, Kummer, E, Seyffer, F, Berynskyy, M, Anstett, B, Zahn, R, Wade, RC, Mogk, A & Bukau, B 2012, 'A tightly regulated molecular toggle controls AAA+ disaggregase', Nature Structural & Molecular Biology, vol. 19, no. 12, pp. 1338-46. https://doi.org/10.1038/nsmb.2441

APA

Oguchi, Y., Kummer, E., Seyffer, F., Berynskyy, M., Anstett, B., Zahn, R., Wade, R. C., Mogk, A., & Bukau, B. (2012). A tightly regulated molecular toggle controls AAA+ disaggregase. Nature Structural & Molecular Biology, 19(12), 1338-46. https://doi.org/10.1038/nsmb.2441

Vancouver

Oguchi Y, Kummer E, Seyffer F, Berynskyy M, Anstett B, Zahn R et al. A tightly regulated molecular toggle controls AAA+ disaggregase. Nature Structural & Molecular Biology. 2012;19(12):1338-46. https://doi.org/10.1038/nsmb.2441

Author

Oguchi, Yuki ; Kummer, Eva ; Seyffer, Fabian ; Berynskyy, Mykhaylo ; Anstett, Benjamin ; Zahn, Regina ; Wade, Rebecca C ; Mogk, Axel ; Bukau, Bernd. / A tightly regulated molecular toggle controls AAA+ disaggregase. In: Nature Structural & Molecular Biology. 2012 ; Vol. 19, No. 12. pp. 1338-46.

Bibtex

@article{bf32f7668c52486882671ec956dda128,
title = "A tightly regulated molecular toggle controls AAA+ disaggregase",
abstract = "The ring-forming AAA+ protein ClpB cooperates with the DnaK chaperone system to refold aggregated proteins in Escherichia coli. The M domain, a ClpB-specific coiled-coil structure with two wings, motif 1 and motif 2, is essential to disaggregation, but the positioning and mechanistic role of M domains in ClpB hexamers remain unresolved. We show that M domains nestle at the ClpB ring surface, with both M-domain motifs contacting the first ATPase domain (AAA-1). Both wings contribute to maintaining a repressed ClpB activity state. Motif 2 docks intramolecularly to AAA-1 to regulate ClpB unfolding power, and motif 1 contacts a neighboring AAA-1 domain. Mutations that stabilize motif 2 docking repress ClpB, whereas destabilization leads to derepressed ClpB activity with greater unfolding power that is toxic in vivo. Our results underline the vital nature of tight ClpB activity control and elucidate a regulated M-domain toggle control mechanism.",
keywords = "Amino Acid Sequence, Endopeptidase Clp, Escherichia coli Proteins/chemistry, Heat-Shock Proteins/chemistry, Molecular Chaperones, Molecular Sequence Data, Mutation, Protein Conformation",
author = "Yuki Oguchi and Eva Kummer and Fabian Seyffer and Mykhaylo Berynskyy and Benjamin Anstett and Regina Zahn and Wade, {Rebecca C} and Axel Mogk and Bernd Bukau",
year = "2012",
doi = "10.1038/nsmb.2441",
language = "English",
volume = "19",
pages = "1338--46",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "nature publishing group",
number = "12",

}

RIS

TY - JOUR

T1 - A tightly regulated molecular toggle controls AAA+ disaggregase

AU - Oguchi, Yuki

AU - Kummer, Eva

AU - Seyffer, Fabian

AU - Berynskyy, Mykhaylo

AU - Anstett, Benjamin

AU - Zahn, Regina

AU - Wade, Rebecca C

AU - Mogk, Axel

AU - Bukau, Bernd

PY - 2012

Y1 - 2012

N2 - The ring-forming AAA+ protein ClpB cooperates with the DnaK chaperone system to refold aggregated proteins in Escherichia coli. The M domain, a ClpB-specific coiled-coil structure with two wings, motif 1 and motif 2, is essential to disaggregation, but the positioning and mechanistic role of M domains in ClpB hexamers remain unresolved. We show that M domains nestle at the ClpB ring surface, with both M-domain motifs contacting the first ATPase domain (AAA-1). Both wings contribute to maintaining a repressed ClpB activity state. Motif 2 docks intramolecularly to AAA-1 to regulate ClpB unfolding power, and motif 1 contacts a neighboring AAA-1 domain. Mutations that stabilize motif 2 docking repress ClpB, whereas destabilization leads to derepressed ClpB activity with greater unfolding power that is toxic in vivo. Our results underline the vital nature of tight ClpB activity control and elucidate a regulated M-domain toggle control mechanism.

AB - The ring-forming AAA+ protein ClpB cooperates with the DnaK chaperone system to refold aggregated proteins in Escherichia coli. The M domain, a ClpB-specific coiled-coil structure with two wings, motif 1 and motif 2, is essential to disaggregation, but the positioning and mechanistic role of M domains in ClpB hexamers remain unresolved. We show that M domains nestle at the ClpB ring surface, with both M-domain motifs contacting the first ATPase domain (AAA-1). Both wings contribute to maintaining a repressed ClpB activity state. Motif 2 docks intramolecularly to AAA-1 to regulate ClpB unfolding power, and motif 1 contacts a neighboring AAA-1 domain. Mutations that stabilize motif 2 docking repress ClpB, whereas destabilization leads to derepressed ClpB activity with greater unfolding power that is toxic in vivo. Our results underline the vital nature of tight ClpB activity control and elucidate a regulated M-domain toggle control mechanism.

KW - Amino Acid Sequence

KW - Endopeptidase Clp

KW - Escherichia coli Proteins/chemistry

KW - Heat-Shock Proteins/chemistry

KW - Molecular Chaperones

KW - Molecular Sequence Data

KW - Mutation

KW - Protein Conformation

U2 - 10.1038/nsmb.2441

DO - 10.1038/nsmb.2441

M3 - Journal article

C2 - 23160353

VL - 19

SP - 1338

EP - 1346

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 12

ER -

ID: 257865385