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@ARTICLE{Sundermeyer:911589,
      author       = {Sundermeyer, Lea and Bosco, Graziella and Gujar, Srushti
                      and Brocker, Melanie and Baumgart, Meike and Willbold,
                      Dieter and Weiergräber, Oliver H. and Bellinzoni, Marco and
                      Bott, Michael},
      title        = {{C}haracteristics of the {G}ln{H} and {G}ln{X} {S}ignal
                      {T}ransduction {P}roteins {C}ontrolling {P}kn{G}-{M}ediated
                      {P}hosphorylation of {O}dh{I} and 2-{O}xoglutarate
                      {D}ehydrogenase {A}ctivity in {C}orynebacterium glutamicum},
      journal      = {Microbiology spectrum},
      volume       = {10},
      number       = {6},
      issn         = {2165-0497},
      address      = {Birmingham, Ala.},
      publisher    = {ASM},
      reportid     = {FZJ-2022-04848},
      pages        = {e02677-22},
      year         = {2022},
      abstract     = {In Corynebacterium glutamicum the protein kinase PknG
                      phosphorylates OdhI and thereby abolishes the inhibition of
                      2-oxoglutarate dehydrogenase activity by unphosphorylated
                      OdhI. Our previous studies suggested that PknG activity is
                      controlled by the periplasmic binding protein GlnH and the
                      transmembrane protein GlnX, because ΔglnH and ΔglnX
                      mutants showed a growth defect on glutamine similar to that
                      of a ΔpknG mutant. We have now confirmed the involvement of
                      GlnH and GlnX in the control of OdhI phosphorylation by
                      analyzing the OdhI phosphorylation status and glutamate
                      secretion in ΔglnH and ΔglnX mutants and by characterizing
                      ΔglnX suppressor mutants. We provide evidence for GlnH
                      being a lipoprotein and show by isothermal titration
                      calorimetry that it binds l-aspartate and l-glutamate with
                      moderate to low affinity, but not l-glutamine, l-asparagine,
                      or 2-oxoglutarate. Based on a structural comparison with
                      GlnH of Mycobacterium tuberculosis, two residues critical
                      for the binding affinity were identified and verified. The
                      predicted GlnX topology with four transmembrane segments and
                      two periplasmic domains was confirmed by PhoA and LacZ
                      fusions. A structural model of GlnX suggested that, with the
                      exception of a poorly ordered N-terminal region, the entire
                      protein is composed of α-helices and small loops or
                      linkers, and it revealed similarities to other bacterial
                      transmembrane receptors. Our results suggest that the
                      GlnH-GlnX-PknG-OdhI-OdhA signal transduction cascade serves
                      to adapt the flux of 2-oxoglutarate between ammonium
                      assimilation via glutamate dehydrogenase and energy
                      generation via the tricarboxylic acid (TCA) cycle to the
                      availability of the amino group donors l-glutamate and
                      l-aspartate in the environment.IMPORTANCE Actinobacteria
                      comprise a large number of species playing important roles
                      in biotechnology and medicine, such as Corynebacterium
                      glutamicum, the major industrial amino acid producer, and
                      Mycobacterium tuberculosis, the pathogen causing
                      tuberculosis. Many actinobacteria use a signal transduction
                      process in which the phosphorylation status of OdhI
                      (corynebacteria) or GarA (mycobacteria) regulates the carbon
                      flux at the 2-oxoglutarate node. Inhibition of
                      2-oxoglutarate dehydrogenase by unphosphorylated OdhI shifts
                      the flux of 2-oxoglutarate from the TCA cycle toward
                      glutamate formation and, thus, ammonium assimilation.
                      Phosphorylation of OdhI/GarA is catalyzed by the protein
                      kinase PknG, whose activity was proposed to be controlled by
                      the periplasmic binding protein GlnH and the transmembrane
                      protein GlnX. In this study, we combined genetic,
                      biochemical, and structural modeling approaches to
                      characterize GlnH and GlnX of C. glutamicum and confirm
                      their roles in the GlnH-GlnX-PknG-OdhI-OdhA signal
                      transduction cascade. These findings are relevant also to
                      other Actinobacteria employing a similar control process.},
      cin          = {IBG-1 / IBI-7},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBG-1-20101118 / I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524) / 2171 - Biological and environmental resources
                      for sustainable use (POF4-217)},
      pid          = {G:(DE-HGF)POF4-5244 / G:(DE-HGF)POF4-2171},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {36445153},
      UT           = {WOS:000891967400001},
      doi          = {10.1128/spectrum.02677-22},
      url          = {https://juser.fz-juelich.de/record/911589},
}