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Nature. 2016 Nov 3;539(7627):48-53. doi: 10.1038/nature20122. Epub 2016 Oct 6.

Arginine phosphorylation marks proteins for degradation by a Clp protease.

Author information

1
Research Institute of Molecular Pathology (IMP), Dr-Bohr-Gasse 7, 1030 Vienna, Austria.
2
Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr-Bohr-Gasse 3, 1030 Vienna, Austria.

Abstract

Protein turnover is a tightly controlled process that is crucial 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 describe 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 demonstrate that arginine phosphorylation by the McsB kinase is required and sufficient for the degradation of substrate proteins. The docking site for phosphoarginine is located in the amino-terminal domain of the ClpC ATPase, as resolved at high resolution in a co-crystal structure. Together, our data demonstrate that phosphoarginine functions as a bona fide degradation tag for the ClpC-ClpP protease. This system, which is widely distributed across Gram-positive bacteria, is functionally analogous to the eukaryotic ubiquitin-proteasome system.

PMID:
27749819
DOI:
10.1038/nature20122
[Indexed for MEDLINE]

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