9DPE

CryoEM Structure of Human BTN2A1 ectodomain in complex with TCR-blocking 2A1.12 Fab

9DPE の概要

• エントリーDOI: 10.2210/pdb9dpe/pdb
• 関連するPDBエントリー: 8VC7
• EMDBエントリー: 47104
• 分子名称: Butyrophilin subfamily 2 member A1, Human IgG1 Fragment Antibody Heavy Chain, Human IgG1 Fragment Antibody Light Chain, ... (5 entities in total)
• 機能のキーワード: complex, antibody, immune recognition, signaling protein, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89731.92

構造登録者

Ramesh, A.,Fuller, J.R.,Roy, S.,Adams, E. (登録日: 2024-09-21, 公開日: 2025-04-23)

主引用文献

Ramesh, A.,Roy, S.,Slezak, T.,Fuller, J.,Graves, H.,Mamedov, M.R.,Marson, A.,Kossiakoff, A.A.,Adams, E.J.
Mapping the extracellular molecular architecture of the pAg-signaling complex with alpha-Butyrophilin antibodies.
Sci Rep, 15:12162-12162, 2025

PubMed Abstract: Target cells trigger Vγ9Vδ2 T cell activation by signaling the intracellular accumulation of phospho-antigen metabolites (pAgs) through Butyrophilin (BTN)-3A1 and BTN2A1 to the Vγ9Vδ2 T cell receptor (TCR). An incomplete understanding of the molecular dynamics in this signaling complex hampers Vγ9Vδ2 T cell immunotherapeutic efficacy. A panel of engineered α-BTN3A1 and α-BTN2A1 antibody (mAb) reagents was used to probe the roles of BTN3A1 and BTN2A1 in pAg signaling. Modified α-BTN3A1 mAbs with increased inter-Fab distances establish that tight clustering of BTN3A1 is not necessary to stimulate Vγ9Vδ2 T cell activation, and that antagonism may occur through occlusion of a critical binding interaction between BTN3A1 and a yet unknown co-receptor. Finally, a panel of additional α-BTN2A1 antagonists utilize different biophysical mechanisms to compete with Vγ9Vδ2 TCRs for BTN2A1 binding. The complex structures of BTN2A1 ectodomain and Fabs from three antagonist mAbs provide molecular insights into BTN2A1 epitopes critical for pAg-signaling.

PubMed: 40204806
DOI: 10.1038/s41598-025-94347-w

実験手法

ELECTRON MICROSCOPY (3.86 Å)