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PMID: 23160353 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A tightly regulated molecular toggle controls AAA+ disaggregase.

Nature structural & molecular biology ·Vol. 19 ·No. 12 ·2012-12-00 ·Pages 1338-46

Oguchi Y, Kummer E, Seyffer F, Berynskyy M, Anstett B, Zahn R, Wade RC, Mogk A, Bukau B

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.

MeSH Terms
Amino Acid Sequence Endopeptidase Clp Escherichia coli Proteins/chemistry,genetics,physiology Heat-Shock Proteins/chemistry,genetics,physiology Molecular Chaperones Molecular Sequence Data Mutation Protein Conformation
Chemicals
Escherichia coli Proteins Heat-Shock Proteins Molecular Chaperones Endopeptidase Clp ClpB protein, E coli
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Oguchi Yuki
Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany.
Kummer Eva
Seyffer Fabian
Berynskyy Mykhaylo
Anstett Benjamin
Zahn Regina
Wade Rebecca C
Mogk Axel
Bukau Bernd
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2441
Published
2012-12-00
Epub
2012-00-18
Pages
1338-46
Language
English
Region
United States
NLM ID
101186374
Subset
IM
External Links
PubMed source DOI: 10.1038/nsmb.2441 View journal details
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