title: Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for kinase PknD.
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 beta-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.
authors.affiliation: Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Pérez
authors.forename: Rósula
authors.initials: R
authors.lastname: Garcia
authors.forename: Horacio
authors.initials: H
authors.lastname: Bach
authors.forename: Jacobus H
authors.initials: JH
authors.lastname: de Waard
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: Yossef
authors.initials: Y
authors.lastname: Av-Gay
authors.forename: Jose
authors.initials: J
authors.lastname: Bubis
authors.forename: Howard E
authors.initials: HE
authors.lastname: Takiff
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000472:pathogenicity; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013379:Substrate Specificity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C514650:MmpL7 protein, Mycobacterium tuberculosis; D011494:Protein Kinases; C112455:PknD protein, Nostoc sp. PCC 7120