 |
PDBsum entry 3ta3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
3ta3
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
267 a.a.
|
|
|
|
|
|
|
|
|
|
|
96 a.a.
|
|
|
|
|
|
|
|
|
|
|
202 a.a.
|
|
|
|
|
|
|
|
|
|
|
239 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Unique interplay between sugar and lipid in determining the antigenic potency of bacterial antigens for nkt cells.
|
|
|
Authors
|
|
E.Girardi,
E.D.Yu,
Y.Li,
N.Tarumoto,
B.Pei,
J.Wang,
P.Illarionov,
Y.Kinjo,
M.Kronenberg,
D.M.Zajonc.
|
|
|
Ref.
|
|
Plos Biol, 2011,
9,
e1001189.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Invariant natural killer T (iNKT) cells are an evolutionary conserved T cell
population characterized by features of both the innate and adaptive immune
response. Studies have shown that iNKT cells are required for protective
responses to Gram-positive pathogens such as Streptococcus pneumoniae, and that
these cells recognize bacterial diacylglycerol antigens presented by CD1d, a
non-classical antigen-presenting molecule. The combination of a lipid backbone
containing an unusual fatty acid, vaccenic acid, as well as a glucose sugar that
is weaker or not stimulatory when linked to other lipids, is required for iNKT
cell stimulation by these antigens. Here we have carried out structural and
biophysical studies that illuminate the reasons for the stringent requirement
for this unique combination. The data indicate that vaccenic acid bound to the
CD1d groove orients the protruding glucose sugar for TCR recognition, and it
allows for an additional hydrogen bond of the glucose with CD1d when in complex
with the TCR. Furthermore, TCR binding causes an induced fit in both the sugar
and CD1d, and we have identified the CD1d amino acids important for iNKT TCR
recognition and the stability of the ternary complex. The studies show also how
hydrogen bonds formed by the glucose sugar can account for the distinct binding
kinetics of the TCR for this CD1d-glycolipid complex. Therefore, our studies
illuminate the mechanism of glycolipid recognition for antigens from important
pathogens.
|
|
|
|
|
|
|
