Stochastic but Highly Coordinated Protein Unfolding and Translocation by the ClpXP Proteolytic Machine
Name
Baker_Stochastic but.pdf
Size
2.16 MB
Format
Adobe PDF
Checksum (MD5)
53f237a26147c02ddb556b1760a3760a
Author(s)
Cordova, Juan Carlos
Aubin-Tam, Marie-Eve
Lang, Matthew J.
Olivares, Adrian O.
Shin, Yongdae
Calmat, Stephane Geraldine Michele
Schmitz, Karl Robert
Baker, Tania
Sauer, Robert T.
Stinson, Benjamin Michael
Date Issued
July 2014
Journal
Cell
Publisher
Elsevier
Citation
Cordova, Juan Carlos et al. “Stochastic but Highly Coordinated Protein Unfolding and Translocation by the ClpXP Proteolytic Machine.” Cell 158.3 (2014): 647–658.
Version
Author's final manuscript
Abstract
ClpXP and other AAA+ proteases recognize, mechanically unfold, and translocate target proteins into a chamber for proteolysis. It is not known whether these remarkable molecular machines operate by a stochastic or sequential mechanism or how power strokes relate to the ATP-hydrolysis cycle. Single-molecule optical trapping allows ClpXP unfolding to be directly visualized and reveals translocation steps of ∼1–4 nm in length, but how these activities relate to solution degradation and the physical properties of substrate proteins remains unclear. By studying single-molecule degradation using different multidomain substrates and ClpXP variants, we answer many of these questions and provide evidence for stochastic unfolding and translocation. We also present a mechanochemical model that accounts for single-molecule, biochemical, and structural results for our observation of enzymatic memory in translocation stepping, for the kinetics of translocation steps of different sizes, and for probabilistic but highly coordinated subunit activity within the ClpX ring.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2014.05.043
