Structure and function of ClpXP, a AAA+ proteolytic machine powered by probabilistic ATP hydrolysis. (4th March 2022)

• Record Type: Journal Article
• Authors: Sauer, Robert T.; Fei, Xue; Bell, Tristan A.; Baker, Tania A.
• Is Part Of: Critical reviews in biochemistry and molecular biology. Volume 57:Number 2(2022)
• Page Start: 188
• Page End: 204
• Publication Date: 2022-03-04
• Subjects: AAA+ proteases -- protein degradation -- molecular machine -- ATP hydrolysis -- ClpX -- ClpP -- cryo-EM; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biochemistry -- Periodicals; Molecular Biology -- Periodicals; Review Literature -- Periodicals; 572
• DOI: 10.1080/10409238.2021.1979461
• Languages: English
• ISSNs: 1040-9238

Abstract

Abstract: ClpXP is an archetypical AAA+ protease, consisting of ClpX and ClpP. ClpX is an ATP-dependent protein unfoldase and polypeptide translocase, whereas ClpP is a self-compartmentalized peptidase. ClpXP is currently the only AAA+ protease for which high-resolution structures exist, the molecular basis of recognition for a protein substrate is understood, extensive biochemical and genetic analysis have been performed, and single-molecule optical trapping has allowed direct visualization of the kinetics of substrate unfolding and translocation. In this review, we discuss our current understanding of ClpXP structure and function, evaluate competing sequential and probabilistic mechanisms of ATP hydrolysis, and highlight open questions for future exploration.