ClpAP

ClpAP is an ATP-dependent protease complex found in many bacteria, composed of ClpA, a AAA+ ATPase, and ClpP, a serine protease core. The complex degrades misfolded or short-lived regulatory proteins, contributing to protein quality control, stress response, and cellular regulation.

ClpP forms a tetradecamer arranged as two stacked heptameric rings that create a proteolytic chamber. ClpA forms a hexameric ring that docks on ClpP, and the interaction is mediated by IGF loops in ClpA that bind hydrophobic pockets on ClpP, enabling substrate translocation into the chamber.

Substrate recognition is aided by adaptor proteins such as ClpS in some bacteria, which directs N-end rule substrates to ClpAP. ATP hydrolysis by ClpA drives substrate unfolding and threading through a narrow pore into ClpP, where proteolysis occurs.

ClpAP degrades misfolded proteins and numerous regulatory proteins, contributing to protein quality control, stress tolerance, and virulence in certain pathogens. Substrate specificity depends on adaptors and cellular context.

The ClpAP system is regulated by cellular energy status and stress signals; defects can reduce viability under stress and affect pathogenicity. As a member of the AAA+ protease family, ClpAP is a potential target for antimicrobial strategies.

Related systems include ClpXP, another protease that uses ClpX as ATPase; both belong to the Clp protease family.