4V1P

BTN3 Structure


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.168 

wwPDB Validation   3D Report Full Report


This is version 1.0 of the entry. See complete history


Literature

Activation of Human Gammadelta T Cells by Cytosolic Interactions of Btn3A1 with Soluble Phosphoantigens and the Cytoskeletal Adaptor Periplakin.

Rhodes, D.A.Chen, H.Price, A.J.Keeble, A.H.Davey, M.S.James, L.C.Eberl, M.Trowsdale, J.

(2015) J Immunol 194: 2390

  • DOI: https://doi.org/10.4049/jimmunol.1401064
  • Primary Citation of Related Structures:  
    4V1P

  • PubMed Abstract: 

    The three butyrophilin BTN3A molecules, BTN3A1, BTN3A2, and BTN3A3, are members of the B7/butyrophilin-like group of Ig superfamily receptors, which modulate the function of T cells. BTN3A1 controls activation of human Vγ9/Vδ2 T cells by direct or indirect presentation of self and nonself phosphoantigens (pAg). We show that the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate binds to the intracellular B30.2 domain of BTN3A1 with an affinity of 1.1 μM, whereas the endogenous pAg isopentenyl pyrophosphate binds with an affinity of 627 μM. Coculture experiments using knockdown cell lines showed that in addition to BTN3A1, BTN3A2 and BTN3A3 transmit activation signals to human γδ T cells in response to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and the aminobisphosphonate drug zoledronate that causes intracellular accumulation of isopentenyl pyrophosphate. The plakin family member periplakin, identified in yeast two-hybrid assays, interacted with a membrane-proximal di-leucine motif, located proximal to the B30.2 domain in the BTN3A1 cytoplasmic tail. Periplakin did not interact with BTN3A2 or BTN3A3, which do not contain the di-leucine motif. Re-expression into a BTN3A1 knockdown line of wild-type BTN3A1, but not of a variant lacking the periplakin binding motif, BTN3A1Δexon5, restored γδ T cell responses, demonstrating a functional role for periplakin interaction. These data, together with the widespread expression in epithelial cells, tumor tissues, and macrophages detected using BTN3A antiserum, are consistent with complex functions for BTN3A molecules in tissue immune surveillance and infection, linking the cell cytoskeleton to γδ T cell activation by indirectly presenting pAg to the Vγ9/Vδ2 TCR.


  • Organizational Affiliation

    Immunology Division, Department of Pathology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 0XY, United Kingdom; dar32@cam.ac.uk.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BUTYROPHILIN SUBFAMILY 3 MEMBER A1188Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O00481 (Homo sapiens)
Explore O00481 
Go to UniProtKB:  O00481
PHAROS:  O00481
GTEx:  ENSG00000026950 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO00481
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.168 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.62α = 90
b = 124.664β = 90
c = 38.822γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2015-07-22 
  • Deposition Author(s): James, L.C.

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-22
    Type: Initial release