Crystal structure of IIGP1: a paradigm for interferon-inducible p47 resistance GTPases

Mol Cell. 2004 Sep 10;15(5):727-39. doi: 10.1016/j.molcel.2004.07.017.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Dimerization
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / genetics
  • Guanosine Triphosphate / metabolism
  • Host-Parasite Interactions / genetics
  • Hydrolysis
  • Immunity, Innate / genetics
  • Interferons / metabolism*
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Mutation / genetics
  • Protein Structure, Tertiary / physiology


  • Guanosine Triphosphate
  • Interferons
  • GTP Phosphohydrolases

Associated data

  • PDB/1TPZ
  • PDB/1TQ2
  • PDB/1TQ4
  • PDB/1TQ6
  • PDB/1TQD