6J7O

Crystal structure of toxin TglT (unusual type guanylyltransferase-like toxin, Rv1045) mutant E146Q from Mycobacterium tuberculosis

Summary for 6J7O

• Entry DOI: 10.2210/pdb6j7o/pdb
• Descriptor: guanylyltransferase-like toxin, MAGNESIUM ION (3 entities in total)
• Functional Keywords: guanylyltransferase;guanylyltransferase-like toxin;ta, toxin
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 1
• Total formula weight: 34516.00

Authors

Yu, X.,Gao, X.,Zhu, K.,Wojdyla, J.A.,Wang, M.,Cui, S. (deposition date: 2019-01-18, release date: 2020-05-13, Last modification date: 2023-11-22)

Primary citation

Yu, X.,Gao, X.,Zhu, K.,Yin, H.,Mao, X.,Wojdyla, J.A.,Qin, B.,Huang, H.,Wang, M.,Sun, Y.C.,Cui, S.
Characterization of a toxin-antitoxin system in Mycobacterium tuberculosis suggests neutralization by phosphorylation as the antitoxicity mechanism.
Commun Biol, 3:216-216, 2020

PubMed Abstract: Mycobacterium tuberculosis (Mtb) encodes an exceptionally large number of toxin-antitoxin (TA) systems, supporting the hypothesis that TA systems are involved in pathogenesis. We characterized the putative Mtb Rv1044-Rv1045 TA locus structurally and functionally, demonstrating that it constitutes a bona fide TA system but adopts a previously unobserved antitoxicity mechanism involving phosphorylation of the toxin. While Rv1045 encodes the guanylyltransferase TglT functioning as a toxin, Rv1044 encodes the novel atypical serine protein kinase TakA, which specifically phosphorylates the cognate toxin at residue S78, thereby neutralizing its toxicity. In contrast to previous predictions, we found that Rv1044-Rv1045 does not belong to the type IV TA family because TglT and TakA interact with each other as substrate and kinase, suggesting an unusual type of TA system. Protein homology analysis suggests that other COG5340-DUF1814 protein pairs, two highly associated but uncharacterized protein families widespread in prokaryotes, might share this unusual antitoxicity mechanism.

PubMed: 32382148
DOI: 10.1038/s42003-020-0941-1

Experimental method

X-RAY DIFFRACTION (1.9 Å)