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PDBsum entry 4kc3
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Immune system
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PDB id
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4kc3
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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 insights into the interaction of il-33 with its receptors.
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Authors
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X.Liu,
M.Hammel,
Y.He,
J.A.Tainer,
U.S.Jeng,
L.Zhang,
S.Wang,
X.Wang.
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Ref.
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Proc Natl Acad Sci U S A, 2013,
110,
14918-14923.
[DOI no: ]
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PubMed id
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Abstract
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Interleukin (IL)-33 is an important member of the IL-1 family that has
pleiotropic activities in innate and adaptive immune responses in host defense
and disease. It signals through its ligand-binding primary receptor ST2 and IL-1
receptor accessory protein (IL-1RAcP), both of which are members of the IL-1
receptor family. To clarify the interaction of IL-33 with its receptors, we
determined the crystal structure of IL-33 in complex with the ectodomain of ST2
at a resolution of 3.27 Å. Coupled with structure-based mutagenesis and binding
assay, the structural results define the molecular mechanism by which ST2
specifically recognizes IL-33. Structural comparison with other ligand-receptor
complexes in the IL-1 family indicates that surface-charge complementarity is
critical in determining ligand-binding specificity of IL-1 primary receptors.
Combined crystallography and small-angle X-ray-scattering studies reveal that
ST2 possesses hinge flexibility between the D3 domain and D1D2 module, whereas
IL-1RAcP exhibits a rigid conformation in the unbound state in solution. The
molecular flexibility of ST2 provides structural insights into domain-level
conformational change of IL-1 primary receptors upon ligand binding, and the
rigidity of IL-1RAcP explains its inability to bind ligands directly. The
solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle
X-ray-scattering analysis resembles IL-1β-IL-1RII-IL-1RAcP and
IL-1β-IL-1RI-IL-1RAcP crystal structures. The collective results confer IL-33
structure-function relationships, supporting and extending a general model for
ligand-receptor assembly and activation in the IL-1 family.
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