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PDBsum entry 6cx7
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Immune system
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PDB id
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6cx7
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Contents |
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202 a.a.
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239 a.a.
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269 a.a.
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97 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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Structure of alpha-gsa[12,6p] bound by cd1d and in complex with the va14vb8.2 tcr
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Structure:
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Chimeric t cell antigen receptor alpha chain va14,va24, ja18. Chain: c. Engineered: yes. Chimeric t cell antigen receptor beta chain vb8.2, vb11. Chain: d. Engineered: yes. Antigen-presenting glycoprotein cd1d1. Chain: a.
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Source:
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Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: cd1d1, mcg_3074. Expressed in: escherichia coli. Expression_system_taxid: 866768. Gene: b2m.
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Resolution:
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2.60Å
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R-factor:
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0.209
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R-free:
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0.239
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Authors:
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J.Wang,D.Zajonc
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Key ref:
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J.Wang
et al.
(2019).
A molecular switch in mouse CD1d modulates natural killer T cell activation by α-galactosylsphingamides.
J Biol Chem,
294,
14345-14356.
PubMed id:
DOI:
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Date:
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02-Apr-18
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Release date:
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10-Apr-19
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PROCHECK
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Headers
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References
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No UniProt id for this chain
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No UniProt id for this chain
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DOI no:
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J Biol Chem
294:14345-14356
(2019)
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PubMed id:
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A molecular switch in mouse CD1d modulates natural killer T cell activation by α-galactosylsphingamides.
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J.Wang,
J.Guillaume,
J.Janssens,
S.G.Remesh,
G.Ying,
A.Bitra,
S.Van Calenbergh,
D.M.Zajonc.
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ABSTRACT
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Type I natural killer T (NKT) cells are a population of innate like T
lymphocytes that rapidly respond to α-GalCer presented by CD1d via the
production of both pro- and anti-inflammatory cytokines. While developing novel
α-GalCer analogs that were meant to be utilized as potential adjuvants because
of their production of pro-inflammatory cytokines (Th1 skewers), we generated
α-galactosylsphingamides (αGSA). Surprisingly, αGSAs are not potent antigens
in vivo despite their strong T-cell receptor (TCR)-binding affinities.
Here, using surface plasmon resonance (SPR), antigen presentation assays, and
X-ray crystallography (yielding crystal structures of 19 different binary
(CD1d-glycolipid) or ternary (CD1d-glycolipid-TCR) complexes at resolutions
between 1.67 and 2.85 Å), we characterized the biochemical and structural
details of αGSA recognition by murine NKT cells. We identified a molecular
switch within murine (m)CD1d that modulates NKT cell activation by αGSAs. We
found that the molecular switch involves a hydrogen bond interaction between
Tyr-73 of mCD1d and the amide group oxygen of αGSAs. We further established
that the length of the acyl chain controls the positioning of the amide group
with respect to the molecular switch and works synergistically with Tyr-73 to
control NKT cell activity. In conclusion, our findings reveal important
mechanistic insights into the presentation and recognition of glycolipids with
polar moieties in an otherwise apolar milieu. These observations may inform the
development αGSAs as specific NKT cell antagonists to modulate immune responses.
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