title: The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion.
abstract: BACKGROUND
  The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization.
  
  
  RESULTS
  We determined the crystal structure of an oligomerization-impaired Irga6 mutant bound to a non-hydrolyzable GTP analog. Contrary to the previous model, the structure shows that the GTPase domains dimerize in a parallel fashion. The nucleotides in the center of the interface participate in dimerization by forming symmetric contacts with each other and with the switch I region of the opposing Irga6 molecule. The latter contact appears to activate GTP hydrolysis by stabilizing the position of the catalytic glutamate 106 in switch I close to the active site. Further dimerization contacts involve switch II, the G4 helix and the trans stabilizing loop.
  
  
  CONCLUSIONS
  The Irga6 structure features a parallel GTPase domain dimer, which appears to be a unifying feature of all dynamin and septin superfamily members. This study contributes important insights into the assembly and catalytic mechanisms of IRG proteins as prerequisite to understand their anti-microbial action.
authors.affiliation: Max-Delbrueck-Centrum for Molecular Medicine, Crystallography, Robert-Rössle-Strasse 10, 13125, Berlin, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schulte
authors.affiliation: Institute for Genetics, Department of Cell Genetics, University of Cologne, Zülpicher Strasse 47a, 50674, Cologne, Germany.|Present address: Bayer Pharma AG, Global Biologics Research, Nattermannallee 1, 50829, Cologne, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pawlowski
authors.affiliation: Max-Delbrueck-Centrum for Molecular Medicine, Crystallography, Robert-Rössle-Strasse 10, 13125, Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Faelber
authors.affiliation: Max-Delbrueck-Centrum for Molecular Medicine, Crystallography, Robert-Rössle-Strasse 10, 13125, Berlin, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Fröhlich
authors.affiliation: Institute for Genetics, Department of Cell Genetics, University of Cologne, Zülpicher Strasse 47a, 50674, Cologne, Germany. jhoward@igc.gulbenkian.pt.|Fundação Calouste Gulbenkian, Instituto Gulbenkian de Ciência, 2781-156, Oeiras, Portugal. jhoward@igc.gulbenkian.pt.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Howard
authors.affiliation: Max-Delbrueck-Centrum for Molecular Medicine, Crystallography, Robert-Rössle-Strasse 10, 13125, Berlin, Germany. oliver.daumke@mdc-berlin.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Daumke
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006868:Hydrolysis; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; C491070:Iigp1 protein, mouse