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PDBsum entry 4mnq
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Immune system
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PDB id
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4mnq
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Contents |
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276 a.a.
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100 a.a.
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200 a.a.
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240 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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T-Cell receptor (tcr)-Peptide specificity overrides affinity-Enhancing tcr-Major histocompatibility complex interactions.
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Authors
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D.K.Cole,
K.M.Miles,
F.Madura,
C.J.Holland,
A.J.Schauenburg,
A.J.Godkin,
A.M.Bulek,
A.Fuller,
H.J.Akpovwa,
P.G.Pymm,
N.Liddy,
M.Sami,
Y.Li,
P.J.Rizkallah,
B.K.Jakobsen,
A.K.Sewell.
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Ref.
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J Biol Chem, 2014,
289,
628-638.
[DOI no: ]
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PubMed id
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Abstract
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αβ T-cell receptors (TCRs) engage antigens using complementarity-determining
region (CDR) loops that are either germ line-encoded (CDR1 and CDR2) or
somatically rearranged (CDR3). TCR ligands compose a presentation platform
(major histocompatibility complex (MHC)) and a variable antigenic component
consisting of a short "foreign" peptide. The sequence of events when
the TCR engages its peptide-MHC (pMHC) ligand remains unclear. Some studies
suggest that the germ line elements of the TCR engage the MHC prior to peptide
scanning, but this order of binding is difficult to reconcile with some TCR-pMHC
structures. Here, we used TCRs that exhibited enhanced pMHC binding as a result
of mutations in either CDR2 and/or CDR3 loops, that bound to the MHC or peptide,
respectively, to dissect the roles of these loops in stabilizing TCR-pMHC
interactions. Our data show that TCR-peptide interactions play a strongly
dominant energetic role providing a binding mode that is both temporally and
energetically complementary with a system requiring positive selection by
self-pMHC in the thymus and rapid recognition of non-self-pMHC in the periphery.
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