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@ARTICLE{Bleffert:907782,
      author       = {Bleffert, Florian and Granzin, Joachim and Caliskan,
                      Muttalip and Schott-Verdugo, Stephan N and Siebers, Meike
                      and Thiele, Björn and Rahme, Laurence G and Felgner,
                      Sebastian and Dörmann, Peter and Gohlke, Holger and
                      Batra-Safferling, Renu and Jaeger, Karl-Erich and Kovacic,
                      Filip},
      title        = {{S}tructural, mechanistic and physiological insights into
                      phospholipase {A}-mediated membrane phospholipid degradation
                      in {P}seudomonas aeruginosa},
      journal      = {eLife},
      volume       = {11},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {FZJ-2022-02211},
      pages        = {e72824},
      year         = {2022},
      abstract     = {Cells steadily adapt their membrane glycerophospholipid
                      (GPL) composition to changing environmental and
                      developmental conditions. While the regulation of membrane
                      homeostasis via GPL synthesis in bacteria has been studied
                      in detail, the mechanisms underlying the controlled
                      degradation of endogenous GPLs remain unknown. Thus far, the
                      function of intracellular phospholipases A (PLAs) in GPL
                      remodeling (Lands cycle) in bacteria is not clearly
                      established. Here, we identified the first cytoplasmic
                      membrane-bound phospholipase A1 (PlaF) from Pseudomonas
                      aeruginosa, which might be involved in the Lands cycle. PlaF
                      is an important virulence factor, as the P. aeruginosa
                      ΔplaF mutant showed strongly attenuated virulence in
                      Galleria mellonella and macrophages. We present a
                      2.0-Å-resolution crystal structure of PlaF, the first
                      structure that reveals homodimerization of a single-pass
                      transmembrane (TM) full-length protein. PlaF dimerization,
                      mediated solely through the intermolecular interactions of
                      TM and juxtamembrane regions, inhibits its activity. The
                      dimerization site and the catalytic sites are linked by an
                      intricate ligand-mediated interaction network, which might
                      explain the product (fatty acid) feedback inhibition
                      observed with the purified PlaF protein. We used molecular
                      dynamics simulations and configurational free energy
                      computations to suggest a model of PlaF activation through a
                      coupled monomerization and tilting of the monomer in the
                      membrane, which constrains the active site cavity into
                      contact with the GPL substrates. Thus, these data show the
                      importance of the PlaF mediated GPL remodeling pathway for
                      virulence and could pave the way for the development of
                      novel therapeutics targeting PlaF.},
      cin          = {IBG-4 / IMET / JSC / IBI-7 / NIC / IBG-2 / IBG-3},
      ddc          = {600},
      cid          = {I:(DE-Juel1)IBG-4-20200403 / I:(DE-Juel1)IMET-20090612 /
                      I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)IBI-7-20200312 /
                      I:(DE-Juel1)NIC-20090406 / I:(DE-Juel1)IBG-2-20101118 /
                      I:(DE-Juel1)IBG-3-20101118},
      pnm          = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
                      (SDLs) and Research Groups (POF4-511) / 2171 - Biological
                      and environmental resources for sustainable use (POF4-217) /
                      5241 - Molecular Information Processing in Cellular Systems
                      (POF4-524) / 2173 - Agro-biogeosystems: controls, feedbacks
                      and impact (POF4-217) / Forschergruppe Gohlke
                      $(hkf7_20200501)$},
      pid          = {G:(DE-HGF)POF4-5111 / G:(DE-HGF)POF4-2171 /
                      G:(DE-HGF)POF4-5241 / G:(DE-HGF)POF4-2173 /
                      $G:(DE-Juel1)hkf7_20200501$},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35536643},
      UT           = {WOS:000804454400001},
      doi          = {10.7554/eLife.72824},
      url          = {https://juser.fz-juelich.de/record/907782},
}