Atypical AAA+ Subunit Packing Creates an Expanded Cavity for Disaggregation by the Protein-Remodeling Factor Hsp104

Petra Wendler, James Shorter, Celia Plisson, Anil G. Cashikar, Susan Lindquist, Helen R. Saibil

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Hsp104, a yeast protein-remodeling factor of the AAA+ (ATPases associated with various cellular activities) superfamily, and its homologs in bacteria and plants mediate cell recovery after severe stress by disaggregating denatured proteins through a poorly understood mechanism. Here, we present cryo-electron microscopy maps and domain fitting of Hsp104 hexamers, revealing an unusual arrangement of AAA+ modules with the prominent coiled-coil domain intercalated between the AAA+ domains. This packing results in a greatly expanded cavity, which is capped at either end by N- and C-terminal domains. The fitted structures as well as mutation of conserved coiled-coil arginines suggest that the coiled-coil domain plays a major role in the extraction of proteins from aggregates, providing conserved residues for key functions in ATP hydrolysis and potentially for substrate interaction. The large cavity could enable the uptake of polypeptide loops without a requirement for exposed N or C termini.

Original languageEnglish
Pages (from-to)1366-1377
Number of pages12
JournalCell
Volume131
Issue number7
DOIs
StatePublished - Dec 28 2007

Keywords

  • CELLBIO
  • PROTEINS

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