7ves: Difference between revisions

Latest revision as of 17:23, 29 November 2023

Crystal Structure of nucleotide-free Irgb6

Structural highlights

7ves is a 1 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 2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TGTP2_MOUSE Involved in innate cell-autonomous resistance to intracellular pathogens, such as Toxoplasma gondii. During avirulent type II T. gondii infection, recruited to the parasitophorous vacuole (PV) membrane, leading to PV vesiculation and rupture, and subsequent digestion of the parasite within the cytosol (PubMed:19265156, PubMed:24563254). Not recruited to virulent type I T. gondii PV membrane (PubMed:19265156). May confer an antiviral state for vesicular stomatitis virus (PubMed:9725230).^[1] ^[2] ^[3]

Publication Abstract from PubMed

The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against Toxoplasma gondii infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by T. gondii and disrupts it. Despite the importance of this process, the molecular mechanisms accounting for PVM recognition by Irgb6 remain elusive because of lack of structural information on Irgb6. Here we report the crystal structures of mouse Irgb6 in the GTP-bound and nucleotide-free forms. Irgb6 exhibits a similar overall architecture to other IRGs in which GTP binding induces conformational changes in both the dimerization interface and the membrane-binding interface. The membrane-binding interface of Irgb6 assumes a unique conformation, composed of N- and C-terminal helical regions forming a phospholipid binding site. In silico docking of phospholipids further revealed membrane-binding residues that were validated through mutagenesis and cell-based assays. Collectively, these data demonstrate a novel structural basis for Irgb6 to recognize T. gondii PVM in a manner distinct from other IRGs.

Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6.,Saijo-Hamano Y, Sherif AA, Pradipta A, Sasai M, Sakai N, Sakihama Y, Yamamoto M, Standley DM, Nitta R Life Sci Alliance. 2021 Nov 9;5(1). pii: 5/1/e202101149. doi:, 10.26508/lsa.202101149. Print 2022 Jan. PMID:34753804^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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 Mar 15;182(6):3775-81. doi: 10.4049/jimmunol.0804190. PMID:19265156 doi:https://dx.doi.org/10.4049/jimmunol.0804190
↑ Ohshima J, Lee Y, Sasai M, Saitoh T, Su Ma J, Kamiyama N, Matsuura Y, Pann-Ghill S, Hayashi M, Ebisu S, Takeda K, Akira S, Yamamoto M. Role of mouse and human autophagy proteins in IFN-gamma-induced cell-autonomous responses against Toxoplasma gondii. J Immunol. 2014 Apr 1;192(7):3328-35. doi: 10.4049/jimmunol.1302822. Epub 2014, Feb 21. PMID:24563254 doi:https://dx.doi.org/10.4049/jimmunol.1302822
↑ 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 Sep 1;161(5):2348-55. PMID:9725230
↑ Saijo-Hamano Y, Sherif AA, Pradipta A, Sasai M, Sakai N, Sakihama Y, Yamamoto M, Standley DM, Nitta R. Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6. Life Sci Alliance. 2021 Nov 9;5(1). pii: 5/1/e202101149. doi:, 10.26508/lsa.202101149. Print 2022 Jan. PMID:34753804 doi:https://dx.doi.org/10.26508/lsa.202101149

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OCA

[1] 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 Mar 15;182(6):3775-81. doi: 10.4049/jimmunol.0804190. PMID:19265156 doi:https://dx.doi.org/10.4049/jimmunol.0804190

[2] Ohshima J, Lee Y, Sasai M, Saitoh T, Su Ma J, Kamiyama N, Matsuura Y, Pann-Ghill S, Hayashi M, Ebisu S, Takeda K, Akira S, Yamamoto M. Role of mouse and human autophagy proteins in IFN-gamma-induced cell-autonomous responses against Toxoplasma gondii. J Immunol. 2014 Apr 1;192(7):3328-35. doi: 10.4049/jimmunol.1302822. Epub 2014, Feb 21. PMID:24563254 doi:https://dx.doi.org/10.4049/jimmunol.1302822

[3] 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 Sep 1;161(5):2348-55. PMID:9725230

[4] Saijo-Hamano Y, Sherif AA, Pradipta A, Sasai M, Sakai N, Sakihama Y, Yamamoto M, Standley DM, Nitta R. Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6. Life Sci Alliance. 2021 Nov 9;5(1). pii: 5/1/e202101149. doi:, 10.26508/lsa.202101149. Print 2022 Jan. PMID:34753804 doi:https://dx.doi.org/10.26508/lsa.202101149

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@@ Line 3: / Line 3: @@
 <StructureSection load='7ves' size='340' side='right'caption='[[7ves]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7ves]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VES FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7ves]] is a 1 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=7VES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VES FirstGlance]. <br>
-</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=7ves FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ves OCA], [https://pdbe.org/7ves PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ves RCSB], [https://www.ebi.ac.uk/pdbsum/7ves PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ves ProSAT]</span></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&#8491;</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=7ves FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ves OCA], [https://pdbe.org/7ves PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ves RCSB], [https://www.ebi.ac.uk/pdbsum/7ves PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ves ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/TGTP2_MOUSE TGTP2_MOUSE]] Involved in innate cell-autonomous resistance to intracellular pathogens, such as Toxoplasma gondii. During avirulent type II T. gondii infection, recruited to the parasitophorous vacuole (PV) membrane, leading to PV vesiculation and rupture, and subsequent digestion of the parasite within the cytosol (PubMed:19265156, PubMed:24563254). Not recruited to virulent type I T. gondii PV membrane (PubMed:19265156). May confer an antiviral state for vesicular stomatitis virus (PubMed:9725230).<ref>PMID:19265156</ref> <ref>PMID:24563254</ref> <ref>PMID:9725230</ref>
+[https://www.uniprot.org/uniprot/TGTP2_MOUSE TGTP2_MOUSE] Involved in innate cell-autonomous resistance to intracellular pathogens, such as Toxoplasma gondii. During avirulent type II T. gondii infection, recruited to the parasitophorous vacuole (PV) membrane, leading to PV vesiculation and rupture, and subsequent digestion of the parasite within the cytosol (PubMed:19265156, PubMed:24563254). Not recruited to virulent type I T. gondii PV membrane (PubMed:19265156). May confer an antiviral state for vesicular stomatitis virus (PubMed:9725230).<ref>PMID:19265156</ref> <ref>PMID:24563254</ref> <ref>PMID:9725230</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Nitta, R]]
+[[Category: Mus musculus]]
-[[Category: Saijo-Hamano, Y]]
+[[Category: Nitta R]]
-[[Category: Sakai, N]]
+[[Category: Saijo-Hamano Y]]
-[[Category: Dynamin superfamily]]
+[[Category: Sakai N]]
-[[Category: Hydrolase]]
-[[Category: Immune system]]
-[[Category: Immunity-related gtpase]]
-[[Category: Irg]]
-[[Category: Irgb6]]
-[[Category: P47 gtpase]]
-[[Category: Tgtp]]

7ves: Difference between revisions

Latest revision as of 17:23, 29 November 2023

Crystal Structure of nucleotide-free Irgb6

Structural highlights

Function

Publication Abstract from PubMed

References

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