 |
PDBsum entry 1ogt
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
1ogt
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Dual, Hla-B27 subtype-Dependent conformation of a self-Peptide.
|
|
|
Authors
|
|
M.Hülsmeyer,
M.T.Fiorillo,
F.Bettosini,
R.Sorrentino,
W.Saenger,
A.Ziegler,
B.Uchanska-Ziegler.
|
|
|
Ref.
|
|
J Exp Med, 2004,
199,
271-281.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709
differ only in residue 116 (Asp vs. His) within the peptide binding groove but
are differentially associated with the autoimmune disease ankylosing spondylitis
(AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The
subtypes also generate differential T cell repertoires as exemplified by
distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The
crystal structures described here show that pVIPR binds in an unprecedented dual
conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5
forms a salt bridge to Asp116, connected with drastically different interactions
between peptide and heavy chain, contrasting with the second, conventional
conformation, which is exclusively found in the case of B*2709. These
subtype-dependent differences in pVIPR binding link the emergence of dissimilar
T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried
Asp116/His116 polymorphism and provide novel insights into peptide presentation
by major histocompatibility antigens.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Hla-B27 subtypes differentially associated with disease exhibit subtle structural alterations.
|
|
|
Authors
|
|
M.Hülsmeyer,
R.C.Hillig,
A.Volz,
M.Rühl,
W.Schröder,
W.Saenger,
A.Ziegler,
B.Uchanska-Ziegler.
|
|
|
Ref.
|
|
J Biol Chem, 2002,
277,
47844-47853.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Figure 1.
Fig. 1. Representative section of the 2F[o]  F[c]
electron density map of B*2709·m9 at 1.09 Å
contoured at 1.5  . The
figure shows the conserved pentagonal hydrogen bonding network
(indicated with dotted lines), which fixes the N terminus of the
peptide to the binding groove.
|
|
Figure 2.
Fig. 2. Overall protein fold and peptide binding groove
of HLA-B*2705·m9 and B*2709·m9. A, ribbon
representation of HLA-B*2709·m9 (HC in blue,  [2]m in
green, peptide as ball-and-stick model in red, and disulfide
bridges and Cys67 in yellow). B, superimposition of the peptide
binding grooves of B*2705·m9, B*2709·m9, and
B*2705·ARA[7] (PDB entry 1hsa). Because the binding
grooves are highly similar, only the backbone of the HC of
B*2705·m9 is depicted (ribbon representation). Peptides
are shown as C[  ]traces,
m9 from B*2705 in blue, m9 from B*2709 in cyan, and ARA[7] in
yellow.
|
|
|
|
|
|
The above figures are
reproduced from the cited reference
with permission from the ASBMB
|
|
|
Secondary reference #2
|
|
|
Title
|
|
The three-Dimensional structure of hla-B27 at 2.1 a resolution suggests a general mechanism for tight peptide binding to mhc.
|
|
|
Authors
|
|
D.R.Madden,
J.C.Gorga,
J.L.Strominger,
D.C.Wiley.
|
|
|
Ref.
|
|
Cell, 1992,
70,
1035-1048.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
