6j0k | pdb_00006j0k
Crystal structure of intracellular B30.2 domain of BTN3A3 mutant in complex with HMBPP
Structural highlights
Function[BT3A3_HUMAN] Plays a role in T-cell responses in the adaptive immune response.[1] Publication Abstract from PubMedHuman Vgamma9Vdelta2 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 Vgamma9Vdelta2 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 gammadelta 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 gammadelta T cell activation. HMBPP binding to butyrophilin doubled the binding force between a gammadelta 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 Vgamma9Vdelta2 T cell activation by phosphoantigen-bound butyrophilin, facilitating immunotherapeutic drug design. A Structural Change in Butyrophilin upon Phosphoantigen Binding Underlies Phosphoantigen-Mediated Vgamma9Vdelta2 T Cell Activation.,Yang Y, Li L, Yuan L, Zhou X, Duan J, Xiao H, Cai N, Han S, Ma X, Liu W, Chen CC, Wang L, Li X, Chen J, Kang N, Chen J, Shen Z, Malwal SR, Liu W, Shi Y, Oldfield E, Guo RT, Zhang Y Immunity. 2019 Mar 14. pii: S1074-7613(19)30083-4. doi:, 10.1016/j.immuni.2019.02.016. PMID:30902636[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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