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

Agnidipta Ghosh, Revathy Uthaiah, Jonathan Howard, Christian Herrmann, Eva Wolf

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)727-739
Number of pages13
JournalMolecular Cell
Volume15
Issue number5
DOIs
StatePublished - Sep 10 2004
Externally publishedYes

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GTP Phosphohydrolases
Interferons
Guanosine Triphosphate
Hydrolysis
Nucleotides

ASJC Scopus subject areas

  • Molecular Biology

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Crystal structure of IIGP1 : A paradigm for interferon-inducible p47 resistance GTPases. / Ghosh, Agnidipta; Uthaiah, Revathy; Howard, Jonathan; Herrmann, Christian; Wolf, Eva.

In: Molecular Cell, Vol. 15, No. 5, 10.09.2004, p. 727-739.

Research output: Contribution to journalArticle

Ghosh, Agnidipta ; Uthaiah, Revathy ; Howard, Jonathan ; Herrmann, Christian ; Wolf, Eva. / Crystal structure of IIGP1 : A paradigm for interferon-inducible p47 resistance GTPases. In: Molecular Cell. 2004 ; Vol. 15, No. 5. pp. 727-739.
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