A Phosphosignaling Adaptor Primes the AAA+ Protease ClpXP to Drive Cell Cycle-Regulated Proteolysis.

ABSTRACT: The response regulator CpdR couples phosphorylation events in Caulobacter crescentus with the AAA+ protease ClpXP to provide punctuated degradation of crucial substrates involved in cell cycle regulation. CpdR functions like an adaptor to alter substrate choice by ClpXP; however, it remains unclear how CpdR influences its multiple targets. Here we show that, unlike canonical ClpXP adaptors, CpdR alone does not strongly bind its substrate. Instead, CpdR binds the N-terminal domain of ClpX and prepares (primes) the unfoldase for substrate engagement. This priming creates a recruitment interface that docks multiple substrates and additional adaptor components. We show that adaptor-dependent priming of ClpX avoids concentration-dependent inhibition that limits traditional scaffolding adaptors.

SUBMITTER: Lau J 

PROVIDER: S-EPMC4490964 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature