ClpXP-mediated Degradation of the TAC Antitoxin is Neutralized by the SecB-like Chaperone in Mycobacterium tuberculosis

JOURNAL OF MOLECULAR BIOLOGY

卷:433

Article

Texier, Pauline¹  Bordes, Patricia¹  Nagpal, Jyotsna²  Sala, Ambre Julie¹  Mansour, Moise¹  Cirinesi, Anne-Marie¹  Xu, Xibing¹  Dougan, David Andrew²  Genevaux, Pierre¹ 

[1] Univ Toulouse, Ctr Biol Integrat CBI, Lab Microbiol & Genet Mol, CNRS,UPS, Toulouse, France

[2] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Genet, Melbourne, Vic 3086, Australia

关键词: Toxin-antitoxin;    HigB1-HigA1;    SecB;    ClpX;    ClpC1;   

DOI  :  10.1016/j.jmb.2021.166815

来源: Elsevier

【 摘 要 】

Bacterial toxin-antitoxin (TA) systems are composed of a deleterious toxin and its antagonistic antitoxin. They are widespread in bacterial genomes and mobile genetic elements, and their functions remain largely unknown. Some TA systems, known as TAC modules, include a cognate SecB-like chaperone that assists the antitoxin in toxin inhibition. Here, we have investigated the involvement of proteases in the activation cycle of the TAC system of the human pathogen Mycobacterium tuberculosis. We show that the deletion of endogenous AAA(+) proteases significantly bypasses the need for a dedicated chaperone and identify the mycobacterial ClpXP1 P2 complex as the main protease involved in TAC antitoxin degradation. In addition, we show that the ClpXP1 P2 degron is located at the extreme C-terminal end of the chaperone addiction (ChAD) region of the antitoxin, demonstrating that ChAD functions as a hub for both chaperone binding and recognition by proteases. (C) 2021 Elsevier Ltd. All rights reserved.

【 授权许可】

Free