Crystal structure of IIGP1: A paradigm for interferon-inducible p47 resistance GTPases Journal Article
| Authors: | Ghosh, A.; Uthaiah, R.; Howard, J.; Herrmann, C.; Wolf, E. |
| Article 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. |
| Keywords: | controlled study; unclassified drug; mutation; interferon; nonhuman; protein domain; mouse; animals; mice; complex formation; carboxy terminal sequence; protein binding; molecular mechanics; amino acid sequence; amino terminal sequence; protein induction; crystal structure; models, molecular; dimerization; crystallography, x-ray; protein structure, tertiary; ras protein; molecular structure; catalysis; protein family; structure analysis; guanosine triphosphate; hydrolysis; oligomerization; molecular model; monomer; gtp phosphohydrolases; nucleotide; guanosine diphosphate; guanosine triphosphatase; dimer; immunity, natural; hydrolysis kinetics; interferons; article; protein iigp1; protein p47; host-parasite relations |
| Journal Title: | Molecular Cell |
| Volume: | 15 |
| Issue: | 5 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2004-09-10 |
| Start Page: | 727 |
| End Page: | 739 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2004.07.017 |
| PROVIDER: | scopus |
| PUBMED: | 15350217 |
| DOI/URL: | |
| Notes: | Mol. Cell -- Cited By (since 1996):29 -- Export Date: 16 June 2014 -- CODEN: MOCEF -- Molecular Sequence Numbers: SWISSPROT: P01112, Q60766, Q61635, Q62293; -- Source: Scopus |
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