Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates
Name
elife-61496-v2.pdf
Description
Published version
Size
2.65 MB
Format
Unknown
Checksum (MD5)
3c27569e342ef6063cc136c0e8247346
Author(s)
Fei, Xue
Bell, Tristan Andrew
Barkow, Sarah R.
Baker, Tania
Sauer, Robert T
Date Issued
2020
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Version
Final published version
Abstract
© 2020, eLife Sciences Publications Ltd. All rights reserved. When ribosomes fail to complete normal translation, all cells have mechanisms to ensure degradation of the resulting partial proteins to safeguard proteome integrity. In E. coli and other eubacteria, the tmRNA system rescues stalled ribosomes and adds an ssrA tag or degron to the C-terminus of the incomplete protein, which directs degradation by the AAA+ ClpXP protease. Here, we present cryo-EM structures of ClpXP bound to the ssrA degron. C-terminal residues of the ssrA degron initially bind in the top of an otherwise closed ClpX axial channel and subsequently move deeper into an open channel. For short-degron protein substrates, we show that unfolding can occur directly from the initial closed-channel complex. For longer-degron substrates, our studies illuminate how ClpXP transitions from specific recognition into a nonspecific unfolding and translocation machine. Many AAA+ proteases and protein-remodeling motors are likely to employ similar multistep recognition and engagement strategies.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/ELIFE.61496
