Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding
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elife-46808-v2.pdf
Description
Published version
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738.59 KB
Format
Adobe PDF
Checksum (MD5)
3e8e5cd2e9ab3ed28ed8dd7e60ed90cb
Author(s)
Bell, Tristan Andrew
Baker, Tania
Sauer, Robert T
Date Issued
June 2019
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Bell, Tristan A., Tania A Baker and Robert T Sauer. “Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding.” eLife, vol. 8, 2019, article e46808 © 2019 The Author(s)
Version
Final published version
Abstract
Most AAA+ remodeling motors denature proteins by pulling on the peptide termini of folded substrates, but it is not well-understood how motors produce grip when resisting a folded domain. Here, at single amino-acid resolution, we identify the determinants of grip by measuring how substrate tail sequences alter the unfolding activity of the unfoldase-protease ClpXP. The seven amino acids abutting a stable substrate domain are key, with residues 2-6 forming a core that contributes most significantly to grip. ClpX grips large hydrophobic and aromatic side chains strongly and small, polar, or charged side chains weakly. Multiple side chains interact with pore loops synergistically to strengthen grip. In combination with recent structures, our results support a mechanism in which unfolding grip is primarily mediated by non-specific van der Waal’s interactions between core side chains of the substrate tail and a subset of YVG loops at the top of the ClpX axial pore.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.7554/ELIFE.46808
