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PDBsum entry 2q86
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Immune system
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PDB id
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2q86
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References listed in PDB file
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Key reference
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Title
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Crystal structures of mouse cd1d-Igb3 complex and its cognate valpha14 t cell receptor suggest a model for dual recognition of foreign and self glycolipids.
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Authors
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D.M.Zajonc,
P.B.Savage,
A.Bendelac,
I.A.Wilson,
L.Teyton.
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Ref.
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J Mol Biol, 2008,
377,
1104-1116.
[DOI no: ]
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PubMed id
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Abstract
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The semi-invariant Valpha14Jalpha18 T cell receptor (TCR) is expressed by
regulatory NKT cells and has the unique ability to recognize chemically diverse
ligands presented by CD1d. The crystal structure of CD1d complexed to a natural,
endogenous ligand, isoglobotrihexosylceramide (iGb3), illustrates the extent of
this diversity when compared to the binding of potent, exogenous ligands, such
as alpha-galactosylceramide (alpha-GalCer). A single mode of recognition for
these two classes of ligands would then appear problematic for a single T cell
receptor. However, the Valpha14 TCR adopts two different conformations in the
crystal where, in one configuration, the presence of a larger cavity between the
two CDR3 regions could accommodate iGb3 and, in the other, a smaller cavity fits
alpha-GalCer more snugly. Alternatively, the extended iGb3 headgroup could be
"squashed" upon docking of the TCR and accommodated between the CD1 and TCR
surfaces. Thus, the same TCR may adopt alternative modes of recognition for
these foreign and self-ligands for NKT cell activation.
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Figure 1.
Fig. 1. A representation of the mCD1d-iGb3 complex (a) and
chemical structures of CD1d ligands (b). a, The self-antigen
iGb3 (yellow) is bound in the hydrophobic binding groove between
the α1 and α2 helices of the CD1d heavy chain (grey) that
associates non-covalently with β[2]-microblobulin (β[2]M,
blue-grey) to form a biological heterodimer. Three of the four
N-linked glycosylation sites (Asn20 (N20), Asn42 and Asn165)
carry well-ordered carbohydrates (grey sticks). The spacer lipid
(C[16], orange) present in the binding groove complements the
short C[8]-alkyl chain of the synthetic ligand iGb3. b, The
chemical structure of short-chain iGb3 is different from that of
cis-tetracosenoyl sulfatide (sulfatide C[24:1]), which it
resembles in the core structure, and the short-chain α-GalCer,
which is dissimilar due to the different anomeric conformation
of the galactose (α-versus β-glycosidic linkage). The terminal
α1-3 linked galactose (red) is not ordered in the crystal
structure and, therefore, not shown in Fig. 1 and Fig. 2).
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Figure 4.
Fig. 4. Low-affinity binding of CD1d-PBS-74 to recombinant
TCR Vα14/2Cβ. (a) Successive dilutions of empty CD1d or
CD1d-PBS-74 were injected over immobilized TCR. Subtraction
(CD1-d-PBS-74 sensorgrams minus empty CD1 sensorgrams) and a 1:1
Langmuir fit of CD1d-PBS-74 binding are presented. (b) Magnified
view of the dissociation phase comparing empty CD1d and
CD1d-PBS-74. (c) Association constants of CD1d-PBS-25 and
CD1d-PBS-74 for Vα14/2Cβ TCR. Measurements were reproduced in
two separate experiments.
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The above figures are
reprinted
from an Open Access publication published by Elsevier:
J Mol Biol
(2008,
377,
1104-1116)
copyright 2008.
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