The BioGRID | PUBLICATION VIEW

	Cell Dec (2007); 131(7):1366-77
Atypical AAA- subunit packing creates an expanded cavity for disaggregation by the protein-remodeling factor Hsp104-
Wendler P, Shorter J, Plisson C, Cashikar AG, Lindquist S, Saibil HR
Department of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, UK-
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-
[PUBMED: 18160044]