In Gram-positive bacteria, the McsB protein arginine kinase is central to protein quality control, labelling aberrant molecules for degradation by the ClpCP protease. Despite its importance for stress response and pathogenicity, it is still elusive how the bacterial degradation labelling is regulated. Here, we delineate the mechanism how McsB targets aberrant proteins during stress conditions. Structural data reveal a self-compartmentalized kinase, in which the active sites are sequestered in a molecular cage. The 'closed' octamer interconverts with other oligomers in a phosphorylation-dependent manner and, contrary to these 'open' forms, preferentially labels unfolded proteins. In vivo data show that heat-shock triggers accumulation of higher-order oligomers, of which the octameric McsB is essential for surviving stress situations. The interconversion of open and closed oligomers represents a distinct regulatory mechanism of a degradation labeler, allowing the McsB kinase to adapt its potentially dangerous enzyme function to the needs of the bacterial cell.
Structure factor amplitudes and Coordinate files have been deposited in the Protein Data Bank under the accession number 6TV6.
- Tim Clausen
- Tim Clausen
- Philipp Kukura
- Nikolas Hundt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- William I Weis, Stanford University School of Medicine, United States
© 2021, Hajdusits et al.
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