A novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore

Shawn C. Massoni, Nicola Evans, Ingo Hantke, Colleen Fenton, James Torpey, Katherine Collins, Ewelina Krysztofinska, Janina Muench, Arjun Thapaliya, Santiago Martinez Lumbreras, Sé Hart Martin, Christopher B. Prior, Kürşad Turgay, Rivka Isaacson, Amy H. Camp*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Bacterial protein degradation machinery, which comprises mix-and-match chaperone-protease pairs, plays vital roles in the bacterial life-cycle, and its manipulation has begun to spark interest as an alternative antimicrobial strategy. ClpC-ClpP (ClpCP) is one such chaperone-protease, recruited by adaptors to specific functions in the Gram positive model bacterium Bacillus subtilis. Using genetic approaches, we have identified a new adaptor protein, YjbA, that recruits ClpCP during sporulation, a developmental process by which B. subtilis can wait out unfavorable environmental conditions by becoming hardy, dormant spores. A knockout of yjbA strongly stimulates gene expression in the developing spore; conversely, aberrant overexpression of yjbA during vegetative growth is toxic. A combination of in vivo and in vitro experiments demonstrates that YjbA and ClpC directly interact, and that this interaction induces ClpC oligomerization and ATPase activity. Finally, a co-crystal structure reveals that YjbA binds to the ClpC N-terminal domain at a location distinct from that bound by the well-characterized adaptor protein MecA, but similar to the interaction site on the Mycobacterium tuberculosis ClpC1 N-terminal domain where bactericidal cyclic peptides bind. Based on these data, we speculate that YjbA induces ClpCP to degrade substrate proteins in the developing spore, thereby facilitating steps towards metabolic dormancy.
Original languageEnglish
JournalbioRxiv
DOIs
Publication statusPublished - 3 Mar 2024

Fingerprint

Dive into the research topics of 'A novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore'. Together they form a unique fingerprint.

Cite this