Structure of the MazF-mt9 toxin, a tRNA-specific endonuclease from Mycobacterium tuberculosis

Ran Chen; Jie Tu; Zhihui Liu; Fanrong Meng; Pinyun Ma; Zhishan Ding; Chengwen Yang; Lei Chen; Xiangyu Deng; Wei Xie

doi:10.1016/j.bbrc.2017.03.132

Structure of the MazF-mt9 toxin, a tRNA-specific endonuclease from Mycobacterium tuberculosis

Biochem Biophys Res Commun. 2017 May 6;486(3):804-810. doi: 10.1016/j.bbrc.2017.03.132. Epub 2017 Mar 25.

Authors

Ran Chen¹, Jie Tu¹, Zhihui Liu², Fanrong Meng², Pinyun Ma², Zhishan Ding¹, Chengwen Yang¹, Lei Chen¹, Xiangyu Deng¹, Wei Xie³

Affiliations

¹ State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, 135 W. Xingang Rd., Guangzhou, Guangdong 510275, People's Republic of China.
² Guangzhou Chest Hospital, 62 HengzhiGang Rd., Guangzhou, Guangdong 510095, People's Republic of China.
³ State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, 135 W. Xingang Rd., Guangzhou, Guangdong 510275, People's Republic of China. Electronic address: xiewei6@mail.sysu.edu.cn.

PMID: 28351618
DOI: 10.1016/j.bbrc.2017.03.132

Abstract

Tuberculosis (TB) is a severe disease caused by Mycobacterium tuberculosis (M. tb) and the well-characterized M. tb MazE/F proteins play important roles in stress adaptation. Recently, the MazF-mt9 toxin has been found to display endonuclease activities towards tRNAs but the mechanism is unknown. We hereby present the crystal structure of apo-MazF-mt9. The enzyme recognizes tRNA^Lys with a central UUU motif within the anticodon loop, but is insensitive to the sequence context outside of the loop. Based on our crystallographic and biochemical studies, we identified key residues for catalysis and proposed the potential tRNA-binding site.

Keywords: Crystal structure; Structure-function; Substrate specificity; Toxin-antitoxin; tRNA endonuclease.

MeSH terms

Amino Acid Sequence
Anticodon / chemistry*
Apoproteins / chemistry*
Apoproteins / genetics
Apoproteins / metabolism
Bacterial Proteins / chemistry*
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Bacterial Toxins / chemistry*
Bacterial Toxins / genetics
Bacterial Toxins / metabolism
Base Sequence
Binding Sites
Cloning, Molecular
Endoribonucleases / chemistry*
Endoribonucleases / genetics
Endoribonucleases / metabolism
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression
Models, Molecular
Mycobacterium tuberculosis / chemistry*
Mycobacterium tuberculosis / enzymology
Mycobacterium tuberculosis / pathogenicity
Nucleic Acid Conformation
Protein Binding
Protein Domains
Protein Structure, Secondary
RNA, Transfer, Lys / chemistry*
RNA, Transfer, Lys / genetics
RNA, Transfer, Lys / metabolism
Recombinant Proteins
Sequence Alignment
Structural Homology, Protein
Structure-Activity Relationship

Substances

Anticodon
Apoproteins
Bacterial Proteins
Bacterial Toxins
RNA, Transfer, Lys
Recombinant Proteins
Endoribonucleases
MazF protein, Mycobacterium tuberculosis