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PDBsum entry 1k5n
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Immune system
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PDB id
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1k5n
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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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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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Abstract
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The reasons for the association of the human major histocompatibility complex
protein HLA-B27 with spondyloarthropathies are unknown. To uncover the
underlying molecular causes, we determined the crystal structures of the
disease-associated B*2705 and the nonassociated B*2709 subtypes complexed with
the same nonapeptide (GRFAAAIAK). Both differ in only one residue (Asp(116) and
His(116), respectively) in the F-pocket that accommodates the peptide C
terminus. Several different effects of the Asp(116) --> His replacement are
observed. The bulkier His(116) induces a movement of peptide C-terminal pLys(9),
allowing the formation of a novel salt bridge to Asp(77), whereas the salt
bridge between pLys(9) and Asp(116) is converted into a hydrogen bond with
His(116). His(116) but not Asp(116) adopts two alternative conformations, one of
which leads to breakage of hydrogen bonds. Water molecules near residue 116
differ with regard to number, position, and contacts made. Furthermore, F-pocket
atoms exhibit higher B-factors in B*2709 than in B*2705, indicating an increased
flexibility of the entire region in the former subtype. These changes induce
subtle peptide conformational alterations that may be responsible for the
immunobiological differences between these HLA-B27 subtypes.
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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
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
47844-47853)
copyright 2002.
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Secondary reference #1
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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 #2
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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 #3
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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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