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PDBsum entry 3c5j
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Membrane protein
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PDB id
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3c5j
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Contents |
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178 a.a.
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182 a.a.
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13 a.a.
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References listed in PDB file
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Key reference
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Title
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The structure of hla-Dr52c: comparison to other hla-Drb3 alleles.
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Authors
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S.Dai,
F.Crawford,
P.Marrack,
J.W.Kappler.
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Ref.
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Proc Natl Acad Sci U S A, 2008,
105,
11893-11897.
[DOI no: ]
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PubMed id
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Abstract
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Class II major histocompatibility complex (MHCII) molecules present antigens to
CD4(+) T cells. In addition to the most commonly studied human MHCII isotype,
HLA-DR, whose beta chain is encoded by the HLA-DRB1 locus, several other
isotypes that use the same alpha chain but have beta chains encoded by other
genes. These other DR molecules also are expressed in antigen-presenting cells
and are known to participate in peptide presentation to T cells and to be
recognized as alloantigens by other T cells. Like some of the HLA-DRB1 alleles,
several of these alternate DR molecules have been associated with specific
autoimmune diseases and T cell hypersensitivity. Here we present the structure
of an HLA-DR molecule (DR52c) containing one of these alternate beta chains
(HLA-DRB3*0301) bound to a self-peptide derived from the Tu elongation factor.
The molecule shares structurally conserved elements with other MHC class II
molecules but has some unique features in the peptide-binding groove. Comparison
of the three major HLA-DBR3 alleles (DR52a, b, and c) suggests that they were
derived from one another by recombination events that scrambled the four major
peptide-binding pockets at peptide positions 1, 4, 6, and 9 but left virtually
no polymorphisms elsewhere in the molecules.
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Figure 2.
DR52c peptide-binding pockets. The α1 domain is shown in
cyan; the β1 domain, in magenta. The Tu peptide is colored as
in Fig. 1. Water molecules deep in the pockets (shown as red
balls) are labeled W0, W1, and W2. (A) Side view of the
solvent-accessible surface (probe radius of 1.4 Å) of the
peptide-binding groove. The peptide is shown as a wire frame.
The β1 helix has been partially cut away for clarity. (B) Top
view of the solvent-accessible surfaces of the four peptide
amino acid-binding pockets (P1, P4, P6, and P9) of DR52c,
showing only the side chains of the four bound residues.
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Figure 3.
The hydrogen-bonding network in the P4 and P6 pockets. The
predicted hydrogen bonds among the atoms are shown as green
dotted lines. The water molecules are shown as red balls. White,
peptide carbon; cyan, α chain carbon; magenta, β chain carbon;
blue, nitrogen; red, oxygen. (A) Details of the hydrogen bond
interactions between P4 Asn and the DR52c. The side chains of
Gln α9, Ser β13, Glu β28, Lys β72, and Gln β74 are shown as
sticks. Three ordered water molecules are labeled W3, W4, and
W5. (B) Details of the peptide-binding pocket P6. The side
chains of P6 Pro and DR52c Asp α66, Asn α69, Glu β9, Tyr β30
and Leu β11 are shown as sticks. Two ordered water molecules
are labeled W1 and W2. (C) A hypothetical network in the P6
pocket occupied by Arg.
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