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==Crystal Structure of IIGP1: a paradigm for interferon inducible p47 resistance GTPases==
==Crystal Structure of IIGP1: a paradigm for interferon inducible p47 resistance GTPases==
<StructureSection load='1tq2' size='340' side='right' caption='[[1tq2]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
<StructureSection load='1tq2' size='340' side='right'caption='[[1tq2]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1tq2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TQ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TQ2 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1tq2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TQ2 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1f5n|1f5n]], [[1dg3|1dg3]], [[1tqd|1tqd]], [[1tpz|1tpz]], [[1tq4|1tq4]], [[1tq6|1tq6]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IIGP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1tq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tq2 OCA], [https://pdbe.org/1tq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tq2 RCSB], [https://www.ebi.ac.uk/pdbsum/1tq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tq2 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tq2 OCA], [http://pdbe.org/1tq2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tq2 RCSB], [http://www.ebi.ac.uk/pdbsum/1tq2 PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/IIGP1_MOUSE IIGP1_MOUSE]] GTPase with low activity. Has higher affinity for GDP than for GTP. Plays a role in resistance to intracellular pathogens. Required for disruption of the parasitophorous vacuole formed following T.gondii infection and subsequent killing of the parasite. Mediates resistance to C.trachomatis infection by targeting bacterial inclusions to autophagosomes for subsequent lysosomal destruction.<ref>PMID:11907101</ref> <ref>PMID:16304607</ref> <ref>PMID:19242543</ref> <ref>PMID:12732635</ref>
[https://www.uniprot.org/uniprot/IIGP1_MOUSE IIGP1_MOUSE] GTPase with low activity. Has higher affinity for GDP than for GTP. Plays a role in resistance to intracellular pathogens. Required for disruption of the parasitophorous vacuole formed following T.gondii infection and subsequent killing of the parasite. Mediates resistance to C.trachomatis infection by targeting bacterial inclusions to autophagosomes for subsequent lysosomal destruction.<ref>PMID:11907101</ref> <ref>PMID:16304607</ref> <ref>PMID:19242543</ref> <ref>PMID:12732635</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tq/1tq2_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tq/1tq2_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1tq2 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
Crystal structure of IIGP1: a paradigm for interferon-inducible p47 resistance GTPases.,Ghosh A, Uthaiah R, Howard J, Herrmann C, Wolf E Mol Cell. 2004 Sep 10;15(5):727-39. PMID:15350217<ref>PMID:15350217</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1tq2" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Large Structures]]
[[Category: Ghosh, A]]
[[Category: Mus musculus]]
[[Category: Herrmann, C]]
[[Category: Ghosh A]]
[[Category: Howard, J]]
[[Category: Herrmann C]]
[[Category: Uthaiah, R]]
[[Category: Howard J]]
[[Category: Wolf, E]]
[[Category: Uthaiah R]]
[[Category: Dimer]]
[[Category: Wolf E]]
[[Category: Gtpase]]
[[Category: Immunology]]
[[Category: Interferon gamma]]
[[Category: Signaling protein]]

Latest revision as of 16:30, 13 March 2024

Crystal Structure of IIGP1: a paradigm for interferon inducible p47 resistance GTPasesCrystal Structure of IIGP1: a paradigm for interferon inducible p47 resistance GTPases

Structural highlights

1tq2 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.7Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IIGP1_MOUSE GTPase with low activity. Has higher affinity for GDP than for GTP. Plays a role in resistance to intracellular pathogens. Required for disruption of the parasitophorous vacuole formed following T.gondii infection and subsequent killing of the parasite. Mediates resistance to C.trachomatis infection by targeting bacterial inclusions to autophagosomes for subsequent lysosomal destruction.[1] [2] [3] [4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Zerrahn J, Schaible UE, Brinkmann V, Guhlich U, Kaufmann SH. The IFN-inducible Golgi- and endoplasmic reticulum- associated 47-kDa GTPase IIGP is transiently expressed during listeriosis. J Immunol. 2002 Apr 1;168(7):3428-36. PMID:11907101
  2. ↑ Martens S, Parvanova I, Zerrahn J, Griffiths G, Schell G, Reichmann G, Howard JC. Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases. PLoS Pathog. 2005 Nov;1(3):e24. Epub 2005 Nov 18. PMID:16304607 doi:10.1371/journal.ppat.0010024
  3. ↑ Al-Zeer MA, Al-Younes HM, Braun PR, Zerrahn J, Meyer TF. IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy. PLoS One. 2009;4(2):e4588. doi: 10.1371/journal.pone.0004588. Epub 2009 Feb 26. PMID:19242543 doi:10.1371/journal.pone.0004588
  4. ↑ Uthaiah RC, Praefcke GJ, Howard JC, Herrmann C. IIGP1, an interferon-gamma-inducible 47-kDa GTPase of the mouse, showing cooperative enzymatic activity and GTP-dependent multimerization. J Biol Chem. 2003 Aug 1;278(31):29336-43. Epub 2003 May 5. PMID:12732635 doi:10.1074/jbc.M211973200

1tq2, resolution 2.70Å

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