Crit Rev Biochem Mol Biol. 2021 Dec 19;1-17. doi: 10.1080/10409238.2021.1979461. Epub 2021 Dec 19.

Structure and function of ClpXP, a AAA+ proteolytic machine powered by probabilistic ATP hydrolysis.

Critical reviews in biochemistry and molecular biology

Robert T Sauer, Xue Fei, Tristan A Bell, Tania A Baker

PMID: 34923891 DOI: 10.1080/10409238.2021.1979461

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.

Keywords: AAA+ proteases; ATP hydrolysis; ClpP; ClpX; cryo-EM; molecular machine; protein degradation

Publication Types

• Journal Article

Grant support

• R01 GM101988/GM/NIGMS NIH HHS/United States
• T32 GM007287/GM/NIGMS NIH HHS/United States
• R01 AI016892/AI/NIAID NIH HHS/United States
• R01 DK115558/DK/NIDDK NIH HHS/United States
• R35 GM141517/GM/NIGMS NIH HHS/United States