Motor Mechanism for Protein Threading through Hsp104
Name
Wendler-2009-Motor Mechanism for Protein Threading through Hsp104.pdf
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2.08 MB
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Author(s)
Wendler, Petra
Shorter, James
Snead, David
Plisson, Celia
Clare, Daniel K.
Saibil, Helen R.
Lindquist, Susan
Date Issued
April 2009
Journal
Molecular Cell
Publisher
Elsevier
Citation
Wendler, Petra et al. “Motor Mechanism for Protein Threading Through Hsp104.” Molecular Cell 34.1 (2009): 81–92. Web. 25 May 2012. © 2009 Elsevier Inc.
Version
Final published version
Abstract
The protein-remodeling machine Hsp104 dissolves amorphous aggregates as well as ordered amyloid assemblies such as yeast prions. Force generation originates from a tandem AAA+ (ATPases associated with various cellular activities) cassette, but the mechanism and allostery of this action remain to be established. Our cryoelectron microscopy maps of Hsp104 hexamers reveal substantial domain movements upon ATP binding and hydrolysis in the first nucleotide-binding domain (NBD1). Fitting atomic models of Hsp104 domains to the EM density maps plus supporting biochemical measurements show how the domain movements displace sites bearing the substrate-binding tyrosine loops. This provides the structural basis for N- to C-terminal substrate threading through the central cavity, enabling a clockwise handover of substrate in the NBD1 ring and coordinated substrate binding between NBD1 and NBD2. Asymmetric reconstructions of Hsp104 in the presence of ATPγS or ATP support sequential rather than concerted ATP hydrolysis in the NBD1 ring.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2009.02.026
