Structural basis for intersubunit signaling in a protein disaggregating machine
10.1073/pnas.1207040109
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

ClpB is a ring-forming, ATP-dependent protein disaggregase that cooperates with the cognate Hsp70 system to recover functional protein from aggregates. How ClpB harnesses the energy of ATP binding and hydrolysis to facilitate the mechanical unfolding of previously aggregated, stress-damaged proteins remains unclear. Here, we present crystal structures of the ClpB D2 domain in the nucleotide-bound and -free states, and the fitted cryoEM structure of the D2 hexamer ring, which provide a structural understanding of the ATP power stroke that drives protein translocation through the ClpB hexamer. We demonstrate that the conformation of the substrate-translocating pore loop is coupled to the nucleotide state of thecissubunit, which is transmitted to the neighboring subunit via a conserved but structurally distinct intersubunit-signaling pathway common to diverse AAA+ machines. Furthermore, we found that an engineered, disulfide cross-linked ClpB hexamer is fully functional biochemically, suggesting that ClpB deoligomerization is not required for protein disaggregation.

Bibliography

Biter, A. B., Lee, S., Sung, N., & Tsai, F. T. F. (2012). Structural basis for intersubunit signaling in a protein disaggregating machine. Proceedings of the National Academy of Sciences, 109(31), 12515–12520.

Authors 4
  1. Amadeo B. Biter (first)
  2. Sukyeong Lee (additional)
  3. Nuri Sung (additional)
  4. Francis T.F. Tsai (additional)
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Dates
Type When
Created 13 years, 1 month ago (July 17, 2012, 9:21 a.m.)
Deposited 1 year, 4 months ago (April 26, 2024, 8:56 p.m.)
Indexed 1 year, 2 months ago (June 22, 2024, 3:51 p.m.)
Issued 13 years, 1 month ago (July 16, 2012)
Published 13 years, 1 month ago (July 16, 2012)
Published Online 13 years, 1 month ago (July 16, 2012)
Published Print 13 years, 1 month ago (July 31, 2012)
Funders 0

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@article{Biter_2012, title={Structural basis for intersubunit signaling in a protein disaggregating machine}, volume={109}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1207040109}, DOI={10.1073/pnas.1207040109}, number={31}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Biter, Amadeo B. and Lee, Sukyeong and Sung, Nuri and Tsai, Francis T.F.}, year={2012}, month=jul, pages={12515–12520} }