A tightly regulated molecular toggle controls AAA plus disaggregase

作者：Oguchi Yuki; Kummer Eva; Seyffer Fabian; Berynskyy Mykhaylo; Anstett Benjamin; Zahn Regina; Wade Rebecca C; Mogk Axel^*; Bukau Bernd

来源：Nature Structural & Molecular Biology, 2012, 19(12): 1338-+.

DOI：10.1038/nsmb.2441

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.

• 出版日期2012-12