title: Crystal structure of IIGP1: a paradigm for interferon-inducible p47 resistance GTPases.
abstract: Interferon-inducible p47 GTPases are critical mediators of cell-autonomous resistance against several intracellular pathogens. Here we present the first crystal structure of a member of this novel GTPase family, IIGP1, in its nucleotide-free, GDP-, and GppNHp-bound form. The structure shows a Ras-like G domain between an N-terminal three-helix bundle and a complex system of C-terminal helices and loops. Sequence comparison and secondary structure prediction suggest the IIGP1 structure to be a valid model for the p47 GTPase family. The IIGP1 crystals contain a noncrystallographic dimer. We show that the dimer is required for cooperative GTP hydrolysis and GTP-dependent oligomerization of IIGP1. We also present the GDP- and GppNHp-bound monomeric structures of two dimer interface mutants. Our structures direct approaches to the analysis of the catalytic mechanism of IIGP1 and provide a coherent basis for structure-function studies aimed at elucidating the mechanistic basis of pathogen resistance caused by these enigmatic GTPases.
authors.affiliation: Department of Structural Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
authors.forename: Agnidipta
authors.initials: A
authors.lastname: Ghosh
authors.forename: Revathy
authors.initials: R
authors.lastname: Uthaiah
authors.forename: Jonathan
authors.initials: J
authors.lastname: Howard
authors.forename: Christian
authors.initials: C
authors.lastname: Herrmann
authors.forename: Eva
authors.initials: E
authors.lastname: Wolf
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D019281:Dimerization; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics; D006160:Guanosine Triphosphate / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000235:genetics; D006868:Hydrolysis; D007113:Immunity, Innate / Q000235:genetics; D007372:Interferons / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D006160:Guanosine Triphosphate; D007372:Interferons; D020558:GTP Phosphohydrolases