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PDBsum entry 4nn7
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Cytokine/cytokine receptor
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PDB id
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4nn7
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Contents |
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108 a.a.
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195 a.a.
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170 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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Structural basis of the proinflammatory signaling complex mediated by tslp.
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Authors
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K.Verstraete,
L.Van schie,
L.Vyncke,
Y.Bloch,
J.Tavernier,
E.Pauwels,
F.Peelman,
S.N.Savvides.
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Ref.
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Nat Struct Biol, 2014,
21,
375-382.
[DOI no: ]
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PubMed id
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Abstract
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Thymic stromal lymphopoietin (TSLP), a cytokine produced by epithelial cells at
barrier surfaces, is pivotal for the development of widespread chronic
inflammatory disorders such as asthma and atopic dermatitis. The structure of
the mouse TSLP-mediated signaling complex reveals how TSLP establishes extensive
interfaces with its cognate receptor (TSLPR) and the shared interleukin 7
receptor α-chain (IL-7Rα) to evoke membrane-proximal receptor-receptor
contacts poised for intracellular signaling. Binding of TSLP to TSLPR is a
mechanistic prerequisite for recruitment of IL-7Rα to the high-affinity ternary
complex, which we propose is coupled to a structural switch in TSLP at the
crossroads of the cytokine-receptor interfaces. Functional interrogation of
TSLP-receptor interfaces points to putative interaction hotspots that could be
exploited for antagonist design. Finally, we derive the structural rationale for
the functional duality of IL-7Rα and establish a consensus for the geometry of
ternary complexes mediated by interleukin 2 (IL-2)-family cytokines.
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