8ADA

Crystal structure of ClpC2 N-terminal domain

8ADA の概要

• エントリーDOI: 10.2210/pdb8ada/pdb
• 分子名称: Uncharacterized protein Rv2667 (2 entities in total)
• 機能のキーワード: clpc2, cyma, n-terminal domain, transcription factor, dna binding protein
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15657.62

構造登録者

Taylor, G.,Cui, H.J.,Leodolter, J.,Giese, C.,Weber-Ban, E. (登録日: 2022-07-08, 公開日: 2023-03-29, 最終更新日: 2024-06-19)

主引用文献

Taylor, G.,Cui, H.,Leodolter, J.,Giese, C.,Weber-Ban, E.
ClpC2 protects mycobacteria against a natural antibiotic targeting ClpC1-dependent protein degradation.
Commun Biol, 6:301-301, 2023

PubMed Abstract: Mycobacterium tuberculosis Clp proteases are targeted by several antitubercular compounds, including cyclomarin A (CymA). CymA exerts its toxicity by binding to AAA + chaperone ClpC1. Here, we show that CymA can also bind a partial homologue of ClpC1, known as ClpC2, and we reveal the molecular basis of these interactions by determining the structure of the M. tuberculosis ClpC2:CymA complex. Furthermore, we show deletion of clpC2 in Mycobacterium smegmatis increases sensitivity to CymA. We find CymA exposure leads to a considerable upregulation of ClpC2 via a mechanism in which binding of CymA to ClpC2 prevents binding of ClpC2 to its own promoter, resulting in upregulation of its own transcription in response to CymA. Our study reveals that ClpC2 not only senses CymA, but that through this interaction it can act as a molecular sponge to counteract the toxic effects of CymA and possibly other toxins targeting essential protease component ClpC1 in mycobacteria.

PubMed: 36944713
DOI: 10.1038/s42003-023-04658-9

実験手法

X-RAY DIFFRACTION (1.996 Å)