5LYG

CRYSTAL STRUCTURE OF INTRACELLULAR B30.2 DOMAIN OF BTN3A1 BOUND TO MALONATE

Summary for 5LYG

• Entry DOI: 10.2210/pdb5lyg/pdb
• Descriptor: Butyrophilin subfamily 3 member A1, 1,2-ETHANEDIOL, MALONATE ION, ... (4 entities in total)
• Functional Keywords: b30.2, butyrophilin, signaling protein
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane ; Single- pass type I membrane protein : O00481
• Total number of polymer chains: 1
• Total formula weight: 21777.70

Authors

Mohammed, F.,Baker, A.T.,Salim, M.,Willcox, B.E. (deposition date: 2016-09-28, release date: 2017-09-13, Last modification date: 2024-05-08)

Primary citation

Salim, M.,Knowles, T.J.,Baker, A.T.,Davey, M.S.,Jeeves, M.,Sridhar, P.,Wilkie, J.,Willcox, C.R.,Kadri, H.,Taher, T.E.,Vantourout, P.,Hayday, A.,Mehellou, Y.,Mohammed, F.,Willcox, B.E.
BTN3A1 Discriminates gamma delta T Cell Phosphoantigens from Nonantigenic Small Molecules via a Conformational Sensor in Its B30.2 Domain.
ACS Chem. Biol., 12:2631-2643, 2017

PubMed Abstract: Human Vγ9/Vδ2 T-cells detect tumor cells and microbial infections by recognizing small phosphorylated prenyl metabolites termed phosphoantigens (P-Ag). The type-1 transmembrane protein Butyrophilin 3A1 (BTN3A1) is critical to the P-Ag-mediated activation of Vγ9/Vδ2 T-cells; however, the molecular mechanisms involved in BTN3A1-mediated metabolite sensing are unclear, including how P-Ag's are discriminated from nonantigenic small molecules. Here, we utilized NMR and X-ray crystallography to probe P-Ag sensing by BTN3A1. Whereas the BTN3A1 immunoglobulin variable domain failed to bind P-Ag, the intracellular B30.2 domain bound a range of negatively charged small molecules, including P-Ag, in a positively charged surface pocket. However, NMR chemical shift perturbations indicated BTN3A1 discriminated P-Ag from nonantigenic small molecules by their ability to induce a specific conformational change in the B30.2 domain that propagated from the P-Ag binding site to distal parts of the domain. These results suggest BTN3A1 selectively detects P-Ag intracellularly via a conformational antigenic sensor in its B30.2 domain and have implications for rational design of antigens for Vγ9/Vδ2-based T-cell immunotherapies.

PubMed: 28862425
DOI: 10.1021/acschembio.7b00694

Experimental method

X-RAY DIFFRACTION (1.6 Å)