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From Proteopedia
Crystal Structure of GTP-bound Irgb6
Structural highlights
FunctionTGTP2_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 PubMedThe 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
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