Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for kinase PknD

Jacqueline Pérez, Rósula Garcia, Horacio Bach, Jacobus H. de Waard, William R. Jacobs, Yossef Av-Gay, Jose Bubis, Howard E. Takiff

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The Mycobacterium tuberculosis serine/threonine protein kinases are attractive potential drug targets, and protein kinase D (PknD) is particularly interesting, as it is autophosphorylated on 11 residues, binds proteins containing forkhead associated domains, and contains a β-propeller motif that likely functions as an anchoring sensor domain. We created a pknD knockout of a clinical M. tuberculosis isolate, and found that on in vitro phosphorylation of cell wall fractions it lacked a family of phosphorylated polypeptides seen in the WT. Mass spectrometry identified the phosphorylated polypeptides as MmpL7, a transporter of the RND family. MmpL7 is essential for virulence, presumably because it transports polyketide virulence factors such as phthiocerol dimycocerosate (PDIM) to the cell wall. Phosphorylation of the MmpL family of transporters has not been previously described, but these results suggest that PknD, and perhaps other serine/threonine kinases, could regulate their critical role in the formation of the M. tuberculosis envelope.

Original languageEnglish (US)
Pages (from-to)6-12
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume348
Issue number1
DOIs
StatePublished - Sep 15 2006

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Phosphorylation
Protein-Serine-Threonine Kinases
Mycobacterium tuberculosis
Phosphotransferases
Cells
Polyketides
Cell Wall
Peptides
Virulence Factors
Propellers
Substrates
Forkhead Transcription Factors
Mass spectrometry
Virulence
Mass Spectrometry
Sensors
Pharmaceutical Preparations
Proteins
protein kinase D
phthiocerol dimycocerosate

Keywords

  • MmpL7
  • Phosphorylation
  • PknD
  • RND transporters
  • Serine/threonine kinases
  • Tuberculosis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for kinase PknD. / Pérez, Jacqueline; Garcia, Rósula; Bach, Horacio; de Waard, Jacobus H.; Jacobs, William R.; Av-Gay, Yossef; Bubis, Jose; Takiff, Howard E.

In: Biochemical and Biophysical Research Communications, Vol. 348, No. 1, 15.09.2006, p. 6-12.

Research output: Contribution to journalArticle

Pérez, Jacqueline ; Garcia, Rósula ; Bach, Horacio ; de Waard, Jacobus H. ; Jacobs, William R. ; Av-Gay, Yossef ; Bubis, Jose ; Takiff, Howard E. / Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for kinase PknD. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 348, No. 1. pp. 6-12.
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