6J0K

Crystal structure of intracellular B30.2 domain of BTN3A3 mutant in complex with HMBPP

Summary for 6J0K

• Entry DOI: 10.2210/pdb6j0k/pdb
• Descriptor: Butyrophilin subfamily 3 member A3, (2E)-4-hydroxy-3-methylbut-2-en-1-yl trihydrogen diphosphate (3 entities in total)
• Functional Keywords: butyrophilin, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 51069.02

Authors

Yang, Y.Y.,Liu, W.D.,Cai, N.N.,Chen, C.C.,Guo, R.T.,Zhang, Y.H. (deposition date: 2018-12-24, release date: 2019-04-03, Last modification date: 2023-11-22)

Primary citation

Yang, Y.,Li, L.,Yuan, L.,Zhou, X.,Duan, J.,Xiao, H.,Cai, N.,Han, S.,Ma, X.,Liu, W.,Chen, C.C.,Wang, L.,Li, X.,Chen, J.,Kang, N.,Chen, J.,Shen, Z.,Malwal, S.R.,Liu, W.,Shi, Y.,Oldfield, E.,Guo, R.T.,Zhang, Y.
A Structural Change in Butyrophilin upon Phosphoantigen Binding Underlies Phosphoantigen-Mediated V gamma 9V delta 2 T Cell Activation.
Immunity, 50:1043-, 2019

PubMed Abstract: Human Vγ9Vδ2 T cells respond to microbial infections and malignancy by sensing diphosphate-containing metabolites called phosphoantigens, which bind to the intracellular domain of butyrophilin 3A1, triggering extracellular interactions with the Vγ9Vδ2 T cell receptor (TCR). Here, we examined the molecular basis of this "inside-out" triggering mechanism. Crystal structures of intracellular butyrophilin 3A proteins alone or in complex with the potent microbial phosphoantigen HMBPP or a synthetic analog revealed key features of phosphoantigens and butyrophilins required for γδ T cell activation. Analyses with chemical probes and molecular dynamic simulations demonstrated that dimerized intracellular proteins cooperate in sensing HMBPP to enhance the efficiency of γδ T cell activation. HMBPP binding to butyrophilin doubled the binding force between a γδ T cell and a target cell during "outside" signaling, as measured by single-cell force microscopy. Our findings provide insight into the "inside-out" triggering of Vγ9Vδ2 T cell activation by phosphoantigen-bound butyrophilin, facilitating immunotherapeutic drug design.

PubMed: 30902636
DOI: 10.1016/j.immuni.2019.02.016

Experimental method

X-RAY DIFFRACTION (2 Å)