Indexed on: 18 Oct '16Published on: 18 Oct '16Published in: Nature
Protein turnover is a tightly controlled process critical for the removal of aberrant polypeptides and for cellular signalling. Whereas ubiquitin marks eukaryotic proteins for proteasomal degradation, a general tagging system for the equivalent bacterial Clp proteases is not known. Here we address the targeting mechanism of the ClpC:ClpP proteolytic complex from Bacillus subtilis. Quantitative affinity proteomics using a ClpP trapping mutant show that proteins phosphorylated on arginine residues are selectively targeted to ClpC:ClpP. In vitro reconstitution experiments reveal that the McsB-mediated arginine phosphorylation is required and sufficient for the degradation of substrate proteins. The docking site for phosphoarginine is located in the N-terminal domain of the ClpC ATPase as resolved at high resolution in a co-crystal structure. Together, our data demonstrate that pArg functions as a bona fide degradation tag for the ClpC:ClpP protease. This system, widely distributed across Gram-positive bacteria, is functionally analogous to the eukaryotic ubiquitin-proteasome system.