5UCT

Mycobacterium tuberculosis toxin MazF-mt6

5UCT の概要

• エントリーDOI: 10.2210/pdb5uct/pdb
• 分子名称: Endoribonuclease MazF3, SULFATE ION (3 entities in total)
• 機能のキーワード: toxin, rnase, tuberculosis, hydrolase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22309.52

構造登録者

Hoffer, E.H.,Dunham, C.M. (登録日: 2016-12-22, 公開日: 2017-03-22, 最終更新日: 2024-11-20)

主引用文献

Hoffer, E.D.,Miles, S.J.,Dunham, C.M.
The structure and function of Mycobacterium tuberculosis MazF-mt6 toxin provide insights into conserved features of MazF endonucleases.
J. Biol. Chem., 292:7718-7726, 2017

PubMed Abstract: Toxin-antitoxin systems are ubiquitous in prokaryotic and archaeal genomes and regulate growth in response to stress. contains at least 36 putative toxin-antitoxin gene pairs, and some pathogens such as have over 90 toxin-antitoxin operons. MazF cleaves free mRNA after encountering stress, and nine MazF family members cleave mRNA, tRNA, or rRNA. Moreover, MazF-mt6 cleaves 23S rRNA Helix 70 to inhibit protein synthesis. The overall tertiary folds of these MazFs are predicted to be similar, and therefore, it is unclear how they recognize structurally distinct RNAs. Here we report the 2.7-Å X-ray crystal structure of MazF-mt6. MazF-mt6 adopts a PemK-like fold but lacks an elongated β1-β2 linker, a region that typically acts as a gate to direct RNA or antitoxin binding. In the absence of an elongated β1-β2 linker, MazF-mt6 is unable to transition between open and closed states, suggesting that the regulation of RNA or antitoxin selection may be distinct from other canonical MazFs. Additionally, a shortened β1-β2 linker allows for the formation of a deep, solvent-accessible, active-site pocket, which may allow recognition of specific, structured RNAs like Helix 70. Structure-based mutagenesis and bacterial growth assays demonstrate that MazF-mt6 residues Asp-10, Arg-13, and Thr-36 are critical for RNase activity and likely catalyze the proton-relay mechanism for RNA cleavage. These results provide further critical insights into how MazF secondary structural elements adapt to recognize diverse RNA substrates.

PubMed: 28298445
DOI: 10.1074/jbc.M117.779306

実験手法

X-RAY DIFFRACTION (2.7 Å)