Insights into structural network responsible for oligomerization and activity of bacterial virulence regulator caseinolytic protease P (ClpP) protein.

ABSTRACT: The barrel-shaped caseinolytic protease P (ClpP) is a main virulence regulator in the bacterial pathogen Staphylococcus aureus (SaClpP). It consists of two heptameric rings forming a homotetradecamer with an inner chamber that houses the 14 active sites. We recently showed that SaClpP is able to adopt a compressed, inactive conformation. We present here the 2.3 Å resolution structure of SaClpP in its closed, active conformation as well as the structure of the S98A mutant. Comprehensive mutational analysis aiming at destabilizing one or the other or both conformations was able to pinpoint key residues involved in this catalytic switch and in the heptamer-heptamer interaction. By probing the active site serine with a covalently modifying β-lactone probe, we could show that the tetradecameric

SUBMITTER: Gersch M 

PROVIDER: S-EPMC3308785 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature