7VEX

Crystal Structure of GTP-bound Irgb6

Summary for 7VEX

• Entry DOI: 10.2210/pdb7vex/pdb
• Descriptor: T-cell-specific guanine nucleotide triphosphate-binding protein 2, GUANOSINE-5'-TRIPHOSPHATE (3 entities in total)
• Functional Keywords: irgb6, irgs, immunity-related gtpase, (ifn)-inducible gtpase, p47 gtpase, tgtp, dynamin superfamily, immune system, hydrolase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 47853.90

Authors

Saijo-Hamano, Y.,Sakai, N.,Nitta, R. (deposition date: 2021-09-10, release date: 2021-11-03, Last modification date: 2023-11-29)

Primary citation

Saijo-Hamano, Y.,Sherif, A.A.,Pradipta, A.,Sasai, M.,Sakai, N.,Sakihama, Y.,Yamamoto, M.,Standley, D.M.,Nitta, R.
Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6.
Life Sci Alliance, 5:-, 2022

PubMed Abstract: The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by 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 PVM in a manner distinct from other IRGs.

PubMed: 34753804
DOI: 10.26508/lsa.202101149

Experimental method

X-RAY DIFFRACTION (1.51 Å)