|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==The GTPase domains of the immunity-related Irga6 dimerize in a parallel head-to-head fashion== | | ==The GTPase domains of the immunity-related Irga6 dimerize in a parallel head-to-head fashion== |
| - | <StructureSection load='5fph' size='340' side='right' caption='[[5fph]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='5fph' size='340' side='right'caption='[[5fph]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5fph]] is a 7 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FPH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FPH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5fph]] is a 7 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=5FPH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FPH 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=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 3.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></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=5fph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fph OCA], [http://pdbe.org/5fph PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fph RCSB], [http://www.ebi.ac.uk/pdbsum/5fph PDBsum]</span></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=5fph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fph OCA], [https://pdbe.org/5fph PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fph RCSB], [https://www.ebi.ac.uk/pdbsum/5fph PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fph ProSAT]</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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Daumke, O]] | + | [[Category: Large Structures]] |
| - | [[Category: Faelber, K]] | + | [[Category: Mus musculus]] |
| - | [[Category: Froehlich, C]] | + | [[Category: Daumke O]] |
| - | [[Category: Howard, J]] | + | [[Category: Faelber K]] |
| - | [[Category: Pawlowski, N]]
| + | [[Category: Froehlich C]] |
| - | [[Category: Schulte, K]]
| + | [[Category: Howard J]] |
| - | [[Category: Dynamin superfamily]] | + | [[Category: Pawlowski N]] |
| - | [[Category: Gmppnp]] | + | [[Category: Schulte K]] |
| - | [[Category: Gtpase]] | + | |
| - | [[Category: Hydrolase]] | + | |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Irg protein]]
| + | |
| - | [[Category: Irga6]]
| + | |
| - | [[Category: Oligomerization]]
| + | |
| Structural highlights
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]
Publication Abstract from PubMed
BACKGROUND: The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization. RESULTS: We determined the crystal structure of an oligomerization-impaired Irga6 mutant bound to a non-hydrolyzable GTP analog. Contrary to the previous model, the structure shows that the GTPase domains dimerize in a parallel fashion. The nucleotides in the center of the interface participate in dimerization by forming symmetric contacts with each other and with the switch I region of the opposing Irga6 molecule. The latter contact appears to activate GTP hydrolysis by stabilizing the position of the catalytic glutamate 106 in switch I close to the active site. Further dimerization contacts involve switch II, the G4 helix and the trans stabilizing loop. CONCLUSIONS: The Irga6 structure features a parallel GTPase domain dimer, which appears to be a unifying feature of all dynamin and septin superfamily members. This study contributes important insights into the assembly and catalytic mechanisms of IRG proteins as prerequisite to understand their anti-microbial action.
The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion.,Schulte K, Pawlowski N, Faelber K, Frohlich C, Howard J, Daumke O BMC Biol. 2016 Mar 2;14:14. doi: 10.1186/s12915-016-0236-7. PMID:26934976[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Schulte K, Pawlowski N, Faelber K, Frohlich C, Howard J, Daumke O. The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion. BMC Biol. 2016 Mar 2;14:14. doi: 10.1186/s12915-016-0236-7. PMID:26934976 doi:http://dx.doi.org/10.1186/s12915-016-0236-7
|
