title: The structure of PknB extracellular PASTA domain from mycobacterium tuberculosis suggests a ligand-dependent kinase activation.
abstract: PknB is a transmembrane Ser/Thr protein kinase that defines and belongs to an ultraconserved kinase subfamily found in Gram-positive bacteria. Essential for Mycobacterium tuberculosis growth, its close homolog in Bacillus subtilis has been linked to exit from dormancy. The kinase possesses an extracellular region composed of a repetition of PASTA domains, believed to bind peptidoglycan fragments that might act as a signaling molecule. We report here the first solution structure of this extracellular region. Small-angle X-ray scattering and nuclear magnetic resonance studies show that the four PASTA domains display an unexpected linear organization, contrary to what is observed in the distant protein PBP2x from Streptococccus pneumoniae where two PASTA domains fold over in a compact structure. We propose a model for PknB activation based on a ligand-dependent dimerization of the extracellular PASTA domains that initiates multiple signaling pathways.
authors.affiliation: Centre National de la Recherche Scientifique UMR 5048, Centre de Biochimie Structurale, 29 rue de Navacelles, 34090 Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Barthe
authors.forename: Galina V
authors.initials: GV
authors.lastname: Mukamolova
authors.forename: Christian
authors.initials: C
authors.lastname: Roumestand
authors.forename: Martin
authors.initials: M
authors.lastname: Cohen-Gonsaud
mesh_terms: D019281:Dimerization; D004789:Enzyme Activation; D008024:Ligands; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D008024:Ligands; D010770:Phosphotransferases; D011494:Protein Kinases; C475060:PknB protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases