4N7I

Crystal Structure of Intracellular B30.2 Domain of BTN3A1

Summary for 4N7I

• Entry DOI: 10.2210/pdb4n7i/pdb
• Related: 4N7U
• Descriptor: Butyrophilin subfamily 3 member A1, GLYCEROL, BETA-MERCAPTOETHANOL, ... (6 entities in total)
• Functional Keywords: butyrophilin, cd277, b30.2, pty/spry, 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: 22235.07

Authors

Sandstrom, A.,Adams, E.J. (deposition date: 2013-10-15, release date: 2014-04-23, Last modification date: 2023-09-20)

Primary citation

Sandstrom, A.,Peigne, C.M.,Leger, A.,Crooks, J.E.,Konczak, F.,Gesnel, M.C.,Breathnach, R.,Bonneville, M.,Scotet, E.,Adams, E.J.
The Intracellular B30.2 Domain of Butyrophilin 3A1 Binds Phosphoantigens to Mediate Activation of Human V gamma 9V delta 2 T Cells.
Immunity, 40:490-500, 2014

PubMed Abstract: In humans, Vγ9Vδ2 T cells detect tumor cells and microbial infections, including Mycobacterium tuberculosis, through recognition of small pyrophosphate containing organic molecules known as phosphoantigens (pAgs). Key to pAg-mediated activation of Vγ9Vδ2 T cells is the butyrophilin 3A1 (BTN3A1) protein that contains an intracellular B30.2 domain critical to pAg reactivity. Here, we have demonstrated through structural, biophysical, and functional approaches that the intracellular B30.2 domain of BTN3A1 directly binds pAg through a positively charged surface pocket. Charge reversal of pocket residues abrogates binding and Vγ9Vδ2 T cell activation. We have also identified a gain-of-function mutation within this pocket that, when introduced into the B30.2 domain of the nonstimulatory BTN3A3 isoform, transfers pAg binding ability and Vγ9Vδ2 T cell activation. These studies demonstrate that internal sensing of changes in pAg metabolite concentrations by BTN3A1 molecules is a critical step in Vγ9Vδ2 T cell detection of infection and tumorigenesis.

PubMed: 24703779
DOI: 10.1016/j.immuni.2014.03.003

Experimental method

X-RAY DIFFRACTION (1.4015 Å)