{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T19:07:42Z","timestamp":1767035262406},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Biol"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The interferon-inducible immunity-related GTPases (IRG proteins\/p47 GTPases) are a distinctive family of GTPases that function as powerful cell-autonomous resistance factors. The IRG protein, Irga6 (IIGP1), participates in the disruption of the vacuolar membrane surrounding the intracellular parasite,<jats:italic>Toxoplasma gondii<\/jats:italic>, through which it communicates with its cellular hosts. Some aspects of the protein's behaviour have suggested a dynamin-like molecular mode of action, in that the energy released by GTP hydrolysis is transduced into mechanical work that results in deformation and ultimately rupture of the vacuolar membrane.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Irga6 forms GTP-dependent oligomers<jats:italic>in vitro<\/jats:italic>and thereby activates hydrolysis of the GTP substrate. In this study we define the catalytic G-domain interface by mutagenesis and present a structural model, of how GTP hydrolysis is activated in Irga6 complexes, based on the substrate-twinning reaction mechanism of the signal recognition particle (SRP) and its receptor (SR\u03b1). In conformity with this model, we show that the bound nucleotide is part of the catalytic interface and that the 3'hydroxyl of the GTP ribose bound to each subunit is essential for<jats:italic>trans<\/jats:italic>-activation of hydrolysis of the GTP bound to the other subunit. We show that both positive and negative regulatory interactions between IRG proteins occur via the catalytic interface. Furthermore, mutations that disrupt the catalytic interface also prevent Irga6 from accumulating on the parasitophorous vacuole membrane of<jats:italic>T. gondii<\/jats:italic>, showing that GTP-dependent Irga6 activation is an essential component of the resistance mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The catalytic interface of Irga6 defined in the present experiments can probably be used as a paradigm for the nucleotide-dependent interactions of all members of the large family of IRG GTPases, both activating and regulatory. Understanding the activation mechanism of Irga6 will help to explain the mechanism by which IRG proteins exercise their resistance function. We find no support from sequence or G-domain structure for the idea that IRG proteins and the SRP GTPases have a common phylogenetic origin. It therefore seems probable, if surprising, that the substrate-assisted catalytic mechanism has been independently evolved in the two protein families.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1741-7007-9-7","type":"journal-article","created":{"date-parts":[[2011,2,8]],"date-time":"2011-02-08T14:53:01Z","timestamp":1297176781000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The activation mechanism of Irga6, an interferon-inducible GTPase contributing to mouse resistance against Toxoplasma gondii"],"prefix":"10.1186","volume":"9","author":[{"given":"Nikolaus","family":"Pawlowski","sequence":"first","affiliation":[]},{"given":"Aliaksandr","family":"Khaminets","sequence":"additional","affiliation":[]},{"given":"Julia P","family":"Hunn","sequence":"additional","affiliation":[]},{"given":"Natasa","family":"Papic","sequence":"additional","affiliation":[]},{"given":"Andreas","family":"Schmidt","sequence":"additional","affiliation":[]},{"given":"Revathy C","family":"Uthaiah","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Lange","sequence":"additional","affiliation":[]},{"given":"Gabriela","family":"Vopper","sequence":"additional","affiliation":[]},{"given":"Sascha","family":"Martens","sequence":"additional","affiliation":[]},{"given":"Eva","family":"Wolf","sequence":"additional","affiliation":[]},{"given":"Jonathan C","family":"Howard","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2011,1,28]]},"reference":[{"key":"430_CR1","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1146\/annurev.cellbio.22.010305.104619","volume":"22","author":"S Martens","year":"2006","unstructured":"Martens S, Howard J: The interferon-inducible GTPases. Annu Rev Cell Dev Biol. 2006, 22: 559-589. 10.1146\/annurev.cellbio.22.010305.104619.","journal-title":"Annu Rev Cell Dev Biol"},{"key":"430_CR2","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1111\/j.1462-5822.2007.00916.x","volume":"9","author":"GA Taylor","year":"2007","unstructured":"Taylor GA: IRG proteins: key mediators of interferon-regulated host resistance to intracellular pathogens. Cell Microbiol. 2007, 9: 1099-1107. 10.1111\/j.1462-5822.2007.00916.x.","journal-title":"Cell Microbiol"},{"key":"430_CR3","volume-title":"Mamm Genome","author":"JP Hunn","year":"2010","unstructured":"Hunn JP, Feng CG, Sher A, Howard JC: The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens. Mamm Genome. 2010"},{"key":"430_CR4","doi-asserted-by":"publisher","first-page":"R92","DOI":"10.1186\/gb-2005-6-11-r92","volume":"6","author":"C Bekpen","year":"2005","unstructured":"Bekpen C, Hunn JP, Rohde C, Parvanova I, Guethlein L, Dunn DM, Glowalla E, Leptin M, Howard JC: The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage. Genome Biol. 2005, 6: R92-10.1186\/gb-2005-6-11-r92.","journal-title":"Genome Biol"},{"key":"430_CR5","doi-asserted-by":"publisher","first-page":"e24","DOI":"10.1371\/journal.ppat.0010024","volume":"1","author":"S Martens","year":"2005","unstructured":"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, 1: e24-10.1371\/journal.ppat.0010024.","journal-title":"PLoS Pathog"},{"key":"430_CR6","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1111\/j.1462-5822.2010.01443.x","volume":"12","author":"A Khaminets","year":"2010","unstructured":"Khaminets A, Hunn JP, Konen-Waisman S, Zhao YO, Preukschat D, Coers J, Boyle JP, Ong YC, Boothroyd JC, Reichmann G, Howard JC: Coordinated Loading of IRG Resistance GTPases on to the Toxoplasma gondii Parasitophorous Vacuole. Cell Microbiol. 2010, 12: 939-961. 10.1111\/j.1462-5822.2010.01443.x.","journal-title":"Cell Microbiol"},{"key":"430_CR7","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1084\/jem.20061318","volume":"203","author":"YM Ling","year":"2006","unstructured":"Ling YM, Shaw MH, Ayala C, Coppens I, Taylor GA, Ferguson DJ, Yap GS: Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages. J Exp Med. 2006, 203: 2063-2071. 10.1084\/jem.20061318.","journal-title":"J Exp Med"},{"key":"430_CR8","doi-asserted-by":"publisher","first-page":"e1000288","DOI":"10.1371\/journal.ppat.1000288","volume":"5","author":"YO Zhao","year":"2009","unstructured":"Zhao YO, Khaminets A, Hunn JP, Howard JC: Disruption of the Toxoplasma gondii parasitophorous vacuole by IFNgamma-inducible immunity-related GTPases (IRG proteins) triggers necrotic cell death. PLoS Pathog. 2009, 5: e1000288-10.1371\/journal.ppat.1000288.","journal-title":"PLoS Pathog"},{"key":"430_CR9","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1038\/emboj.2008.176","volume":"27","author":"JP Hunn","year":"2008","unstructured":"Hunn JP, Koenen-Waisman S, Papic N, Schroeder N, Pawlowski N, Lange R, Kaiser F, Zerrahn J, Martens S, Howard JC: Regulatory interactions between IRG resistance GTPases in the cellular response to Toxoplasma gondii. Embo J. 2008, 27: 2495-2509. 10.1038\/emboj.2008.176.","journal-title":"Embo J"},{"key":"430_CR10","doi-asserted-by":"publisher","first-page":"32143","DOI":"10.1074\/jbc.M804846200","volume":"283","author":"N Papic","year":"2008","unstructured":"Papic N, Hunn JP, Pawlowski N, Zerrahn J, Howard JC: Inactive and Active States of the Interferon-inducible Resistance GTPase, Irga6, in Vivo. J Biol Chem. 2008, 283: 32143-32151. 10.1074\/jbc.M804846200.","journal-title":"J Biol Chem"},{"key":"430_CR11","doi-asserted-by":"publisher","first-page":"29336","DOI":"10.1074\/jbc.M211973200","volume":"278","author":"RC Uthaiah","year":"2003","unstructured":"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, 278: 29336-29343. 10.1074\/jbc.M211973200.","journal-title":"J Biol Chem"},{"key":"430_CR12","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrm1313","volume":"5","author":"GJ Praefcke","year":"2004","unstructured":"Praefcke GJ, McMahon HT: The dynamin superfamily: universal membrane tubulation and fission molecules?. Nat Rev Mol Cell Biol. 2004, 5: 133-147. 10.1038\/nrm1313.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"430_CR13","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1002\/bies.201000086","volume":"32","author":"N Pawlowski","year":"2010","unstructured":"Pawlowski N: Dynamin self-assembly and the vesicle scission mechanism: How dynamin oligomers cleave the membrane neck of clathrin-coated pits during endocytosis. Bioessays. 2010, 32: 1033-1039. 10.1002\/bies.201000086.","journal-title":"Bioessays"},{"key":"430_CR14","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.molcel.2004.07.017","volume":"15","author":"A Ghosh","year":"2004","unstructured":"Ghosh A, Uthaiah R, Howard J, Herrmann C, Wolf E: Crystal structure of IIGP1: a paradigm for interferon-inducible p47 resistance GTPases. Mol Cell. 2004, 15: 727-739. 10.1016\/j.molcel.2004.07.017.","journal-title":"Mol Cell"},{"key":"430_CR15","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/341209a0","volume":"341","author":"EF Pai","year":"1989","unstructured":"Pai EF, Kabsch W, Krengel U, Holmes KC, John J, Wittinghofer A: Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature. 1989, 341: 209-214. 10.1038\/341209a0.","journal-title":"Nature"},{"key":"430_CR16","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/349117a0","volume":"349","author":"HR Bourne","year":"1991","unstructured":"Bourne HR, Sanders DA, McCormick F: The GTPase superfamily: conserved structure and molecular mechanism. Nature. 1991, 349: 117-127. 10.1038\/349117a0.","journal-title":"Nature"},{"key":"430_CR17","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1126\/science.1062023","volume":"294","author":"IR Vetter","year":"2001","unstructured":"Vetter IR, Wittinghofer A: The guanine nucleotide-binding switch in three dimensions. Science. 2001, 294: 1299-1304. 10.1126\/science.1062023.","journal-title":"Science"},{"key":"430_CR18","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.4049\/jimmunol.161.12.6715","volume":"161","author":"U Boehm","year":"1998","unstructured":"Boehm U, Guethlein L, Klamp T, Ozbek K, Schaub A, Futterer A, Pfeffer K, Howard JC: Two families of GTPases dominate the complex cellular response to IFN-gamma. J Immunol. 1998, 161: 6715-6723.","journal-title":"J Immunol"},{"key":"430_CR19","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.4049\/jimmunol.173.4.2594","volume":"173","author":"S Martens","year":"2004","unstructured":"Martens S, Sabel K, Lange R, Uthaiah R, Wolf E, Howard JC: Mechanisms regulating the positioning of mouse p47 resistance GTPases LRG-47 and IIGP1 on cellular membranes: retargeting to plasma membrane induced by phagocytosis. J Immunol. 2004, 173: 2594-2606.","journal-title":"J Immunol"},{"key":"430_CR20","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nature02250","volume":"427","author":"PF Egea","year":"2004","unstructured":"Egea PF, Shan SO, Napetschnig J, Savage DF, Walter P, Stroud RM: Substrate twinning activates the signal recognition particle and its receptor. Nature. 2004, 427: 215-221. 10.1038\/nature02250.","journal-title":"Nature"},{"key":"430_CR21","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1090827","volume":"303","author":"PJ Focia","year":"2004","unstructured":"Focia PJ, Shepotinovskaya IV, Seidler JA, Freymann DM: Heterodimeric GTPase core of the SRP targeting complex. Science. 2004, 303: 373-377. 10.1126\/science.1090827.","journal-title":"Science"},{"key":"430_CR22","doi-asserted-by":"publisher","first-page":"e1000576","DOI":"10.1371\/journal.pbio.1000576","volume":"8","author":"T Steinfeldt","year":"2010","unstructured":"Steinfeldt T, K\u00f6nen-Waisman S, Tong L, Pawlowski N, Lamkemeyer T, Sibley LD, Hunn JP, Howard JC: Phosphorylation of mouse immunity-related GTPase (IRG) resistance proteins is an evasion strategy for virulent toxoplasma gondii. PLoS Biol. 2010, 8: e1000576-10.1371\/journal.pbio.1000576.","journal-title":"PLoS Biol"},{"key":"430_CR23","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/385361a0","volume":"385","author":"DM Freymann","year":"1997","unstructured":"Freymann DM, Keenan RJ, Stroud RM, Walter P: Structure of the conserved GTPase domain of the signal recognition particle. Nature. 1997, 385: 361-364. 10.1038\/385361a0.","journal-title":"Nature"},{"key":"430_CR24","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/385365a0","volume":"385","author":"G Montoya","year":"1997","unstructured":"Montoya G, Svensson C, Luirink J, Sinning I: Crystal structure of the NG domain from the signal-recognition particle receptor FtsY. Nature. 1997, 385: 365-368. 10.1038\/385365a0.","journal-title":"Nature"},{"key":"430_CR25","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1006\/jmbi.1999.3427","volume":"295","author":"JR Jagath","year":"2000","unstructured":"Jagath JR, Rodnina MV, Wintermeyer W: Conformational changes in the bacterial SRP receptor FtsY upon binding of guanine nucleotides and SRP. J Mol Biol. 2000, 295: 745-753. 10.1006\/jmbi.1999.3427.","journal-title":"J Mol Biol"},{"key":"430_CR26","doi-asserted-by":"publisher","first-page":"11339","DOI":"10.1073\/pnas.94.21.11339","volume":"94","author":"C Moser","year":"1997","unstructured":"Moser C, Mol O, Goody RS, Sinning I: The signal recognition particle receptor of Escherichia coli (FtsY) has a nucleotide exchange factor built into the GTPase domain. Proc Natl Acad Sci USA. 1997, 94: 11339-11344. 10.1073\/pnas.94.21.11339.","journal-title":"Proc Natl Acad Sci USA"},{"key":"430_CR27","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1126\/science.7660124","volume":"269","author":"T Powers","year":"1995","unstructured":"Powers T, Walter P: Reciprocal stimulation of GTP hydrolysis by two directly interacting GTPases. Science. 1995, 269: 1422-1424. 10.1126\/science.7660124.","journal-title":"Science"},{"key":"430_CR28","doi-asserted-by":"publisher","first-page":"6214","DOI":"10.1021\/bi0500980","volume":"44","author":"SO Shan","year":"2005","unstructured":"Shan SO, Walter P: Molecular crosstalk between the nucleotide specificity determinant of the SRP GTPase and the SRP receptor. Biochemistry. 2005, 44: 6214-6222. 10.1021\/bi0500980.","journal-title":"Biochemistry"},{"key":"430_CR29","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1006\/jmbi.2001.5378","volume":"317","author":"DD Leipe","year":"2002","unstructured":"Leipe DD, Wolf YI, Koonin EV, Aravind L: Classification and evolution of P-loop GTPases and related ATPases. J Mol Biol. 2002, 317: 41-72. 10.1006\/jmbi.2001.5378.","journal-title":"J Mol Biol"},{"key":"430_CR30","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/nrm2689","volume":"10","author":"R Gasper","year":"2009","unstructured":"Gasper R, Meyer S, Gotthardt K, Sirajuddin M, Wittinghofer A: It takes two to tango: regulation of G proteins by dimerization. Nat Rev Mol Cell Biol. 2009, 10: 423-429. 10.1038\/nrm2689.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"430_CR31","doi-asserted-by":"publisher","first-page":"6696","DOI":"10.1021\/bi9006989","volume":"48","author":"SO Shan","year":"2009","unstructured":"Shan SO, Schmid SL, Zhang X: Signal recognition particle (SRP) and SRP receptor: a new paradigm for multistate regulatory GTPases. Biochemistry. 2009, 48: 6696-6704. 10.1021\/bi9006989.","journal-title":"Biochemistry"},{"key":"430_CR32","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/nature06173","volume":"449","author":"O Daumke","year":"2007","unstructured":"Daumke O, Lundmark R, Vallis Y, Martens S, Butler PJ, McMahon HT: Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling. Nature. 2007, 449: 923-927. 10.1038\/nature06173.","journal-title":"Nature"},{"key":"430_CR33","doi-asserted-by":"publisher","first-page":"31308","DOI":"10.1074\/jbc.M704850200","volume":"282","author":"PA Hubbard","year":"2007","unstructured":"Hubbard PA, Padovani D, Labunska T, Mahlstedt SA, Banerjee R, Drennan CL: Crystal structure and mutagenesis of the metallochaperone MeaB: insight into the causes of methylmalonic aciduria. J Biol Chem. 2007, 282: 31308-31316. 10.1074\/jbc.M704850200.","journal-title":"J Biol Chem"},{"key":"430_CR34","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1038\/sj.emboj.7601171","volume":"25","author":"A Scrima","year":"2006","unstructured":"Scrima A, Wittinghofer A: Dimerisation-dependent GTPase reaction of MnmE: how potassium acts as GTPase-activating element. Embo J. 2006, 25: 2940-2951. 10.1038\/sj.emboj.7601171.","journal-title":"Embo J"},{"key":"430_CR35","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nature06052","volume":"449","author":"M Sirajuddin","year":"2007","unstructured":"Sirajuddin M, Farkasovsky M, Hauer F, Kuhlmann D, Macara IG, Weyand M, Stark H, Wittinghofer A: Structural insight into filament formation by mammalian septins. Nature. 2007, 449: 311-315. 10.1038\/nature06052.","journal-title":"Nature"},{"key":"430_CR36","doi-asserted-by":"publisher","first-page":"20299","DOI":"10.1073\/pnas.1010322107","volume":"107","author":"D Schwefel","year":"2010","unstructured":"Schwefel D, Frohlich C, Eichhorst J, Wiesner B, Behlke J, Aravind L, Daumke O: Structural basis of oligomerization in septin-like GTPase of immunity-associated protein 2 (GIMAP2). Proc Natl Acad Sci USA. 2010, 107: 20299-20304. 10.1073\/pnas.1010322107.","journal-title":"Proc Natl Acad Sci USA"},{"key":"430_CR37","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/nature05312","volume":"444","author":"HH Low","year":"2006","unstructured":"Low HH, Lowe J: A bacterial dynamin-like protein. Nature. 2006, 444: 766-769. 10.1038\/nature05312.","journal-title":"Nature"},{"key":"430_CR38","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/nsb744","volume":"9","author":"YJ Sun","year":"2002","unstructured":"Sun YJ, Forouhar F, Li Hm HM, Tu SL, Yeh YH, Kao S, Shr HL, Chou CC, Chen C, Hsiao CD: Crystal structure of pea Toc34, a novel GTPase of the chloroplast protein translocon. Nat Struct Biol. 2002, 9: 95-100. 10.1038\/nsb744.","journal-title":"Nat Struct Biol"},{"key":"430_CR39","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/sj.emboj.7600530","volume":"24","author":"TA Leonard","year":"2005","unstructured":"Leonard TA, Butler PJ, Lowe J: Bacterial chromosome segregation: structure and DNA binding of the Soj dimer--a conserved biological switch. Embo J. 2005, 24: 270-282. 10.1038\/sj.emboj.7600530.","journal-title":"Embo J"},{"key":"430_CR40","doi-asserted-by":"publisher","first-page":"27492","DOI":"10.1074\/jbc.M600809200","volume":"281","author":"R Gasper","year":"2006","unstructured":"Gasper R, Scrima A, Wittinghofer A: Structural insights into HypB, a GTP-binding protein that regulates metal binding. J Biol Chem. 2006, 281: 27492-27502. 10.1074\/jbc.M600809200.","journal-title":"J Biol Chem"},{"key":"430_CR41","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/387370a0","volume":"387","author":"H Schindelin","year":"1997","unstructured":"Schindelin H, Kisker C, Schlessman JL, Howard JB, Rees DC: Structure of ADP \u00d7 AIF4(-)-stabilized nitrogenase complex and its implications for signal transduction. Nature. 1997, 387: 370-376. 10.1038\/387370a0.","journal-title":"Nature"},{"key":"430_CR42","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nature04510","volume":"440","author":"A Ghosh","year":"2006","unstructured":"Ghosh A, Praefcke GJ, Renault L, Wittinghofer A, Herrmann C: How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP. Nature. 2006, 440: 101-104. 10.1038\/nature04510.","journal-title":"Nature"},{"key":"430_CR43","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/nature09032","volume":"465","author":"JS Chappie","year":"2010","unstructured":"Chappie JS, Acharya S, Leonard M, Schmid SL, Dyda F: G domain dimerization controls dynamin's assembly-stimulated GTPase activity. Nature. 2010, 465: 435-440. 10.1038\/nature09032.","journal-title":"Nature"},{"key":"430_CR44","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1126\/science.277.5324.333","volume":"277","author":"K Scheffzek","year":"1997","unstructured":"Scheffzek K, Ahmadian MR, Kabsch W, Wiesmuller L, Lautwein A, Schmitz F, Wittinghofer A: The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science. 1997, 277: 333-338. 10.1126\/science.277.5324.333.","journal-title":"Science"},{"key":"430_CR45","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0092-8674(00)80204-4","volume":"89","author":"JJ Tesmer","year":"1997","unstructured":"Tesmer JJ, Berman DM, Gilman AG, Sprang SR: Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. Cell. 1997, 89: 251-261. 10.1016\/S0092-8674(00)80204-4.","journal-title":"Cell"},{"key":"430_CR46","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature02505","volume":"429","author":"O Daumke","year":"2004","unstructured":"Daumke O, Weyand M, Chakrabarti PP, Vetter IR, Wittinghofer A: The GTPase-activating protein Rap1GAP uses a catalytic asparagine. Nature. 2004, 429: 197-201. 10.1038\/nature02505.","journal-title":"Nature"},{"key":"430_CR47","doi-asserted-by":"publisher","first-page":"e320","DOI":"10.1371\/journal.pbio.0020320","volume":"2","author":"SO Shan","year":"2004","unstructured":"Shan SO, Stroud RM, Walter P: Mechanism of association and reciprocal activation of two GTPases. PLoS Biol. 2004, 2: e320-10.1371\/journal.pbio.0020320.","journal-title":"PLoS Biol"},{"key":"430_CR48","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/415662a","volume":"415","author":"MJ Seewald","year":"2002","unstructured":"Seewald MJ, Korner C, Wittinghofer A, Vetter IR: RanGAP mediates GTP hydrolysis without an arginine finger. Nature. 2002, 415: 662-666. 10.1038\/415662a.","journal-title":"Nature"},{"key":"430_CR49","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/emboj.2008.30","volume":"27","author":"A Scrima","year":"2008","unstructured":"Scrima A, Thomas C, Deaconescu D, Wittinghofer A: The Rap-RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues. Embo J. 2008, 27: 1145-1153. 10.1038\/emboj.2008.30.","journal-title":"Embo J"},{"key":"430_CR50","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.4049\/jimmunol.0804190","volume":"182","author":"Y Zhao","year":"2009","unstructured":"Zhao Y, Ferguson DJ, Wilson DC, Howard JC, Sibley LD, Yap GS: Virulent Toxoplasma gondii evade immunity-related GTPase-mediated parasite vacuole disruption within primed macrophages. J Immunol. 2009, 182: 3775-3781. 10.4049\/jimmunol.0804190.","journal-title":"J Immunol"},{"key":"430_CR51","doi-asserted-by":"publisher","first-page":"e14","DOI":"10.1371\/journal.ppat.0030014","volume":"3","author":"H El Hajj","year":"2007","unstructured":"El Hajj H, Lebrun M, Arold ST, Vial H, Labesse G, Dubremetz JF: ROP18 is a rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii. PLoS Pathog. 2007, 3: e14-10.1371\/journal.ppat.0030014.","journal-title":"PLoS Pathog"},{"key":"430_CR52","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1126\/science.1133643","volume":"314","author":"S Taylor","year":"2006","unstructured":"Taylor S, Barragan A, Su C, Fux B, Fentress SJ, Tang K, Beatty WL, Hajj HE, Jerome M, Behnke MS, White M, Wootton JC, Sibley LD: A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science. 2006, 314: 1776-1780. 10.1126\/science.1133643.","journal-title":"Science"},{"key":"430_CR53","doi-asserted-by":"publisher","first-page":"3428","DOI":"10.4049\/jimmunol.168.7.3428","volume":"168","author":"J Zerrahn","year":"2002","unstructured":"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, 168: 3428-3436.","journal-title":"J Immunol"},{"key":"430_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0079-6107(96)00015-6","volume":"66","author":"C Herrmann","year":"1996","unstructured":"Herrmann C, Nassar N: Ras and its effectors. Prog Biophys Mol Biol. 1996, 66: 1-41. 10.1016\/S0079-6107(96)00015-6.","journal-title":"Prog Biophys Mol Biol"},{"key":"430_CR55","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.161.5.2348","volume":"161","author":"DA Carlow","year":"1998","unstructured":"Carlow DA, Teh SJ, Teh HS: Specific antiviral activity demonstrated by TGTP, a member of a new family of interferon-induced GTPases. J Immunol. 1998, 161: 2348-2355.","journal-title":"J Immunol"},{"key":"430_CR56","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0166-6851(97)00227-2","volume":"91","author":"HG Fischer","year":"1998","unstructured":"Fischer HG, Stachelhaus S, Sahm M, Meyer HE, Reichmann G: GRA7, an excretory 29 kDa Toxoplasma gondii dense granule antigen released by infected host cells. Mol Biochem Parasitol. 1998, 91: 251-262. 10.1016\/S0166-6851(97)00227-2.","journal-title":"Mol Biochem Parasitol"},{"key":"430_CR57","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1177\/002215549804601210","volume":"46","author":"A Bonhomme","year":"1998","unstructured":"Bonhomme A, Maine GT, Beorchia A, Burlet H, Aubert D, Villena I, Hunt J, Chovan L, Howard L, Brojanac S, Sheu M, Tyner J, Pluot M, Pinon JM: Quantitative immunolocalization of a P29 protein (GRA7), a new antigen of toxoplasma gondii. J Histochem Cytochem. 1998, 46: 1411-1422.","journal-title":"J Histochem Cytochem"},{"key":"430_CR58","doi-asserted-by":"publisher","first-page":"2714","DOI":"10.1002\/elps.1150181505","volume":"18","author":"N Guex","year":"1997","unstructured":"Guex N, Peitsch MC: SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 1997, 18: 2714-2723. 10.1002\/elps.1150181505.","journal-title":"Electrophoresis"},{"key":"430_CR59","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1107\/S0907444998003254","volume":"54","author":"AT Brunger","year":"1998","unstructured":"Brunger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse-Kunstleve RW, Jiang JS, Kuszewski J, Nilges M, Pannu NS, Read RJ, Rice LM, Simonson T, Warren GL: Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr. 1998, 54: 905-921. 10.1107\/S0907444998003254.","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"430_CR60","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/0022-2836(71)90324-X","volume":"55","author":"B Lee","year":"1971","unstructured":"Lee B, Richards FM: The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971, 55: 379-400. 10.1016\/0022-2836(71)90324-X.","journal-title":"J Mol Biol"},{"key":"430_CR61","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","volume":"23","author":"MA Larkin","year":"2007","unstructured":"Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG: Clustal W and Clustal X version 2.0. Bioinformatics. 2007, 23: 2947-2948. 10.1093\/bioinformatics\/btm404.","journal-title":"Bioinformatics"},{"key":"430_CR62","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1093\/bioinformatics\/19.1.163","volume":"19","author":"F Glaser","year":"2003","unstructured":"Glaser F, Pupko T, Paz I, Bell RE, Bechor-Shental D, Martz E, Ben-Tal N: ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics. 2003, 19: 163-164. 10.1093\/bioinformatics\/19.1.163.","journal-title":"Bioinformatics"},{"key":"430_CR63","doi-asserted-by":"publisher","first-page":"W299","DOI":"10.1093\/nar\/gki370","volume":"33","author":"M Landau","year":"2005","unstructured":"Landau M, Mayrose I, Rosenberg Y, Glaser F, Martz E, Pupko T, Ben-Tal N: ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res. 2005, 33: W299-302. 10.1093\/nar\/gki370.","journal-title":"Nucleic Acids Res"}],"container-title":["BMC Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1741-7007-9-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:30:31Z","timestamp":1685939431000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbiol.biomedcentral.com\/articles\/10.1186\/1741-7007-9-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,28]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["430"],"URL":"https:\/\/doi.org\/10.1186\/1741-7007-9-7","relation":{},"ISSN":["1741-7007"],"issn-type":[{"value":"1741-7007","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,28]]},"assertion":[{"value":"14 October 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"7"}}