MapB protein is the essential methionine aminopeptidase in mycobacterium tuberculosis

Miriam Vanunu, Patrick Schall, Tali Haviv Reingewertz, Pradip K. Chakraborti, Bernhard Grimm, Daniel Barkan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

M. tuberculosis (Mtb), which causes tuberculosis disease, continues to be a major global health threat. Correct identification of valid drug targets is important for the development of novel therapeutics that would shorten the current 6–9 month treatment regimen and target resistant bacteria. Methionine aminopeptidases (MetAP), which remove the N-terminal methionine from newly synthesized proteins, are essential in all life forms (eukaryotes and prokaryotes). The MetAPs contribute to the cotranslational control of proteins as they determine their half life (N-terminal end rule) and facilitate further modifications such as acetylation and others. Mtb (and M. bovis) possess two MetAP isoforms, MetAP1a and MetAP1c, encoded by the mapA and mapB genes, respectively. Conflicting evidence was reported in the literature on which of the two variants is essential. To resolve this question, we performed a targeted genetic deletion of each of these two genes. We show that a deletion mutant of mapA is viable with only a weak growth defect. In contrast, we provide two lines of genetic evidence that mapB is indispensable. Furthermore, construction of double-deletion mutants as well as the introduction of point mutations into mapB resulting in proteins with partial activity showed partial, but not full, redundancy between mapB and mapA.We propose that it is MetAP1c (mapB) that is essentially required for mycobacteria and discuss potential reasons for its vitality.

Original languageAmerican English
Article number393
JournalCells
Volume8
Issue number5
DOIs
StatePublished - May 2019

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Gene essentiality
  • Methionine aminopeptidase
  • Mycobacteria
  • Ribosome
  • Tuberculosis

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