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@ARTICLE{Viegas:874256,
      author       = {Viegas, Aldino and Dollinger, Peter and Verma, Neha and
                      Kubiak, Jakub and Viennet, Thibault and Seidel, Claus A. M.
                      and Gohlke, Holger and Etzkorn, Manuel and Kovacic, Filip
                      and Jaeger, Karl-Erich},
      title        = {{S}tructural and dynamic insights revealing how lipase
                      binding domain {MD}1 of {P}seudomonas aeruginosa foldase
                      affects lipase activation},
      journal      = {Scientific reports},
      volume       = {10},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {FZJ-2020-01347},
      pages        = {3578},
      year         = {2020},
      abstract     = {Folding and cellular localization of many proteins of
                      Gram-negative bacteria rely on a network of chaperones and
                      secretion systems. Among them is the lipase-specific foldase
                      Lif, a membrane-bound steric chaperone that tightly binds
                      (KD = 29 nM) and mediates folding of the lipase LipA,
                      a virulence factor of the pathogenic bacterium P.
                      aeruginosa. Lif consists of five-domains, including a mini
                      domain MD1 essential for LipA folding. However, the
                      molecular mechanism of Lif-assisted LipA folding remains
                      elusive. Here, we show in in vitro experiments using a
                      soluble form of Lif (sLif) that isolated MD1 inhibits
                      sLif-assisted LipA activation. Furthermore, the ability to
                      activate LipA is lost in the variant sLifY99A, in which the
                      evolutionary conserved amino acid Y99 from helix α1 of MD1
                      is mutated to alanine. This coincides with an approximately
                      three-fold reduced affinity of the variant to LipA together
                      with increased flexibility of sLifY99A in the complex as
                      determined by polarization-resolved fluorescence
                      spectroscopy. We have solved the NMR solution structures of
                      P. aeruginosa MD1 and variant MD1Y99A revealing a similar
                      fold indicating that a structural modification is likely not
                      the reason for the impaired activity of variant sLifY99A.
                      Molecular dynamics simulations of the sLif:LipA complex in
                      connection with rigidity analyses suggest a long-range
                      network of interactions spanning from Y99 of sLif to the
                      active site of LipA, which might be essential for LipA
                      activation. These findings provide important details about
                      the putative mechanism for LipA activation and point to a
                      general mechanism of protein folding by multi-domain steric
                      chaperones.},
      cin          = {JSC / NIC / ICS-6 / IBG-1 / IMET},
      ddc          = {600},
      cid          = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
                      I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)IBG-1-20101118 /
                      I:(DE-Juel1)IMET-20090612},
      pnm          = {511 - Computational Science and Mathematical Methods
                      (POF3-511) / Forschergruppe Gohlke $(hkf7_20170501)$ /
                      Conformational dynamics of the unbound lipase-specific
                      foldase Lif $(hdd16_20161101)$ / Analysis of the
                      conformational changes during activation of lipase A by its
                      foldase $(hdd16_20171101)$ / 581 - Biotechnology (POF3-581)},
      pid          = {G:(DE-HGF)POF3-511 / $G:(DE-Juel1)hkf7_20170501$ /
                      $G:(DE-Juel1)hdd16_20161101$ / $G:(DE-Juel1)hdd16_20171101$
                      / G:(DE-HGF)POF3-581},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32107397},
      UT           = {WOS:000563068600012},
      doi          = {10.1038/s41598-020-60093-4},
      url          = {https://juser.fz-juelich.de/record/874256},
}