9j5j

Cryo-EM structure of BTN2A1-BTN3A1-BTN3A2 in complex with gdTCR

spinqualitylabelsall models 9j5j, resolution 4.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9j5j is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.05Å Ligands: BMA, H6P, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BT2A1_HUMAN Publication Abstract from PubMed Phosphoantigens (pAgs), produced by infected or cancer cells, trigger the assembly of a membrane receptor complex comprising butyrophilin (BTN) members BTN3A1 and BTN2A1, leading to the activation of gammadelta T cells. BTN3A2 or BTN3A3 forms heteromers with BTN3A1, exhibiting higher gammadelta T cell receptor (TCR)-stimulating activity than BTN3A1 homomers. Cryoelectron microscopy (cryo-EM) structure reveals a pAg-induced BTN2A1-BTN3A1 heterotetramer with a 2:2 stoichiometry, stabilized by interactions between the intracellular B30.2 domains and the extracellular immunoglobulin V (IgV) domains. BTN3A2 or BTN3A3 heterodimerizes with BTN3A1, forming a pAg-induced tetrameric complex with BTN2A1. However, BTN3A1 heterodimers are more stable than BTN3A1 homodimers in this interaction. Cryo-EM reveals that BTN2A1-BTN3A1-BTN3A2 binds two gammadelta TCR ectodomains, with one being sandwiched between the IgV domains of BTN2A1 and BTN3A2, while the other interacts with the free BTN2A1 IgV in the complex, as evidenced by functional data. Together, our findings uncover the mechanism of ligand-induced inside-out stabilization of BTN receptor complexes for dimeric activation of gammadelta TCR. Phosphoantigen-induced inside-out stabilization of butyrophilin receptor complexes drives dimerization-dependent gammadelta TCR activation.,Zhu Y, Gao W, Zheng J, Bai Y, Tian X, Huang T, Lu Z, Dong D, Zhang A, Guo C, Huang Z Immunity. 2025 Apr 30:S1074-7613(25)00175-X. doi: 10.1016/j.immuni.2025.04.012. PMID:40334665 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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