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PDBsum entry 1fzj
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Immune system
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PDB id
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1fzj
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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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The crystal structures of k(bm1) and k(bm8) reveal that subtle changes in the peptide environment impact thermostability and alloreactivity.
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Authors
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M.G.Rudolph,
J.A.Speir,
A.Brunmark,
N.Mattsson,
M.R.Jackson,
P.A.Peterson,
L.Teyton,
I.A.Wilson.
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Ref.
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Immunity, 2001,
14,
231-242.
[DOI no: ]
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PubMed id
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Abstract
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The K(bm1) and K(bm8) natural mutants of the murine MHC class I molecule H-2K(b)
were originally identified by allograft rejection. They also bind viral peptides
VSV8 and SEV9 with high affinity, but their peptide complexes have substantially
decreased thermostability, and the K(bm1) complexes do not elicit alloreactive T
cell responses. Crystal structures of the four mutant complexes at 1.7-1.9 A
resolution are similar to the corresponding wild-type K(b) structures, except in
the vicinity of the mutated residues, which alter the electrostatic potential,
topology, hydrogen bonding, and local water structure of the peptide binding
groove. Thus, these natural K(b) mutations define the minimal perturbations in
the peptide environment that alter antigen presentation to T cells and abolish
alloreactivity.
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Figure 1.
Figure 1. Molecular Structure of K^b and Location of the
Mutations in K^bm1 and K^bm8(A) Ribbon diagram of wild-type K^b
with peptide (magenta) bound in an extended conformation within
the binding groove formed by the α helices and the β sheet
floor.(B) Mutated side chains in K^bm1 and K^bm8 are shown in
green and orange, respectively, while wild-type side chains are
shown in (A).(C) Superimposed Cα tracings of the α[1]α[2]
helices of K^b-VSV8 (yellow), K^b-SEV9 (blue), K^bm1-VSV8
(magenta), K^bm1-SEV9 (red), K^bm8-VSV8 (cyan), and K^bm8-SEV9
(green). Peptide-contacting side chains from the helices, some
of which have different conformations in the six complexes, are
shown
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Figure 5.
Figure 5. Comparison of the Interactions at the K^bm8
Mutation Site with K^bThe coloring scheme is the same as in
Figure 4 except that the MHC residues at the mutation site are
colored orange. The two conformers of Ser-24 in K^bm8-VSV8 are
shown in orange and blue. Note the intricate hydrogen bond
networks mediated by water molecules at the K^bm8 mutation sites
compared to the equivalent wild-type K^b complexes
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The above figures are
reprinted
by permission from Cell Press:
Immunity
(2001,
14,
231-242)
copyright 2001.
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