Structure of the central Staphylococcus aureus AAA+ protease MecA/ClpC/ClpP

<p dir="ltr">This is a chimeraX session associated to the publication "Structure of the central Staphylococcus aureus AAA+ protease MecA/ClpC/ClpP". Abstract: Bacterial AAA+ proteases, like ClpC/ClpP, are ATP-powered degradation machines essential for stress response and virulence. ClpC works with adaptor proteins such as MecA, which enhance substrate threading and ClpC ATPase activity. We present the cryo-EM structure of the MecA/ClpC/ClpP complex from <i>Staphylococcus aureus</i>, showing MecA forming a crown on top of ClpC/ClpP, likely regulating substrate access. ClpC and ClpP interact via two distinct sites: P-loops on ClpC bind hydrophobic ClpP pockets, while ClpP N-terminal β-hairpins insert into the ClpC central channel. These interactions are asymmetric and activity-dependent. ClpC binding shifts ClpP into the proteolytically active state, while ClpP enhances ClpC ATPase and threading activity in a β-hairpin dependent manner. These findings demonstrate a reciprocal allosteric regulation between ClpC and ClpP and uncover key principles of ATPase–peptidase coordination in bacterial AAA+ proteases.</p><p dir="ltr">The entrance is also related to the EMDB, pdb and EMPIAR codes: EMD-51367, EMD-51498, EMD-53538, EMD-53879; pdb:9GI1, 9GOQ, 9R2S and 9RAI; EMPIAR code EMPIAR-12887.</p><p dir="ltr"><br></p><p dir="ltr">The session includes a low-resolution unrymmetrised structure of the adaptor protein MecA in complex with the ClpC ATPase N-terminal and coil-coiled domains. Fitted to the map are multiple predictions of the complex obtained usding eother AlphaFold2 or 3. Please refer to the paper for further explanation.</p>