A tightly regulated molecular toggle controls AAA+ disaggregase

Research output: Contribution to journalJournal articleResearchpeer-review

  • Yuki Oguchi
  • Kummer, Eva
  • Fabian Seyffer
  • Mykhaylo Berynskyy
  • Benjamin Anstett
  • Regina Zahn
  • Rebecca C Wade
  • Axel Mogk
  • Bernd Bukau

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.

Original languageEnglish
JournalNature Structural & Molecular Biology
Issue number12
Pages (from-to)1338-46
Number of pages9
Publication statusPublished - 2012
Externally publishedYes

    Research areas

  • Amino Acid Sequence, Endopeptidase Clp, Escherichia coli Proteins/chemistry, Heat-Shock Proteins/chemistry, Molecular Chaperones, Molecular Sequence Data, Mutation, Protein Conformation

ID: 257865385