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PDBsum entry 1jgd
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Immune system
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PDB id
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1jgd
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Thermodynamic and structural analysis of peptide- And allele-Dependent properties of two hla-B27 subtypes exhibiting differential disease association.
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Authors
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R.C.Hillig,
M.Hülsmeyer,
W.Saenger,
K.Welfle,
R.Misselwitz,
H.Welfle,
C.Kozerski,
A.Volz,
B.Uchanska-Ziegler,
A.Ziegler.
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Ref.
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J Biol Chem, 2004,
279,
652-663.
[DOI no: ]
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PubMed id
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Abstract
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Selected HLA-B27 subtypes are associated with spondyloarthropathies, but the
underlying mechanism is not understood. To explain this association in molecular
terms, a comparison of peptide-dependent dynamic and structural properties of
the differentially disease-associated subtypes HLA-B*2705 and HLA-B*2709 was
carried out. These molecules differ only by a single amino acid at the floor of
the peptide binding groove. The thermostabilities of a series of HLA-B27
molecules complexed with nonameric and decameric peptides were determined and
revealed substantial differences depending on the subtype as well as the
residues at the termini of the peptides. In addition we present the crystal
structure of the B*2709 subtype complexed with a decameric peptide. This
structure provides an explanation for the preference of HLA-B27 for a peptide
with an N-terminal arginine as secondary anchor and the lack of preference for
tyrosine as peptide C terminus in B*2709. The data show that differences in
thermodynamic properties between peptide-complexed HLA-B27 subtypes are
correlated with a variety of structural properties.
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Figure 2.
FIG. 2. Peptide electron density and differential
conformations in the HLA-B27 binding groove. A, electron density
map for the s10R peptide (F[o] - F[c] omit map, contoured at 3
 ,
for the final model with the peptide omitted from map
calculation). Superimposition of peptide binding grooves of
HLA-B27 protein complexes in the top (B) and side view (C)
orientation, with the C  backbone conformation
for s10R (red), m9 (blue, from B^*2709·m9, PDB entry 1k5n
[PDB]
; cyan, from B^*2705·m9, PDB entry 1jge [PDB]
), and ARA[7] (yellow, B^*2705·ARA[7], PDB entry 1hsa [PDB]
), illustrating the stronger bulging of s10R out of the binding
groove. In C, helix 2 is omitted for
clarity.
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Figure 7.
FIG. 7. HLA-B27-specific sandwich coordination of the
secondary anchor pArg1. A, stereo figure showing the clamp stack
involving pArg1 of the s10R peptide (red) and Arg-62, Glu-163,
and Trp167 from the HC (green). The alternative conformation of
Glu-163 is indicated in light green. Hydrogen bonds between
Arg-62, Glu-163, pArg1, and Wat58 are indicated with dotted
lines, and  - -stacking and hydrophobic
interactions by are indicated by stripes. B, the same region in
the B^*2709·m9 complex (PDB entry 1jge [PDB]
). Because the N-terminal pArg1 is missing in m9, no stacking is
present. Consequently, Trp-167 folds onto pGly1, and the Arg-62
side chain adopts a conformation parallel to helix 1. C and
D, for comparison two murine MHC molecules are shown. Both
feature a pArg1 but do not adopt the Arg-62-pArg1-Trp-167
sandwich conformation found in B^*2709·s10R. C,
H-2Kb·VSV8, PDB entry 1bqh [PDB]
, molecule 2. D, H-2D^d·HIV-1 (human immunodeficiency
virus 1), PDB entry 1bii [PDB]
.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
652-663)
copyright 2004.
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Secondary reference #1
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Title
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Hla-B27 subtypes differentially associated with disease exhibit subtle structural alterations.
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Authors
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M.Hülsmeyer,
R.C.Hillig,
A.Volz,
M.Rühl,
W.Schröder,
W.Saenger,
A.Ziegler,
B.Uchanska-Ziegler.
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Ref.
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J Biol Chem, 2002,
277,
47844-47853.
[DOI no: ]
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PubMed id
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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.
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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.
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The above figures are
reproduced from the cited reference
with permission from the ASBMB
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Secondary reference #2
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Title
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Identification of a novel hla-B27 subtype by restriction analysis of a cytotoxic gamma delta t cell clone.
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Authors
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P.Del porto,
M.D'Amato,
M.T.Fiorillo,
L.Tuosto,
E.Piccolella,
R.Sorrentino.
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Ref.
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J Immunol, 1994,
153,
3093-3100.
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PubMed id
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Secondary reference #3
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Title
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The structure of hla-B27 reveals nonamer self-Peptides bound in an extended conformation.
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Authors
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D.R.Madden,
J.C.Gorga,
J.L.Strominger,
D.C.Wiley.
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Ref.
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Nature, 1991,
353,
321-325.
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PubMed id
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Secondary reference #4
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Title
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The three-Dimensional structure of hla-B27 at 2.1 a resolution suggests a general mechanism for tight peptide binding to mhc.
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Authors
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D.R.Madden,
J.C.Gorga,
J.L.Strominger,
D.C.Wiley.
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Ref.
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Cell, 1992,
70,
1035-1048.
[DOI no: ]
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PubMed id
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