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PDBsum entry 4bv4
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Immune system
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PDB id
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4bv4
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References listed in PDB file
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Key reference
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Title
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Cytokine spatzle binds to the drosophila immunoreceptor toll with a neurotrophin-Like specificity and couples receptor activation.
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Authors
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M.Lewis,
C.J.Arnot,
H.Beeston,
A.Mccoy,
A.E.Ashcroft,
N.J.Gay,
M.Gangloff.
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Ref.
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Proc Natl Acad Sci U S A, 2013,
110,
20461-20466.
[DOI no: ]
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PubMed id
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Abstract
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Drosophila Toll functions in embryonic development and innate immunity and is
activated by an endogenous ligand, Spätzle (Spz). The related Toll-like
receptors in vertebrates also function in immunity but are activated directly by
pathogen-associated molecules such as bacterial endotoxin. Here, we present the
crystal structure at 2.35-Å resolution of dimeric Spz bound to a Toll
ectodomain encompassing the first 13 leucine-rich repeats. The cystine knot of
Spz binds the concave face of the Toll leucine-rich repeat solenoid in an area
delineated by N-linked glycans and induces a conformational change. Mutagenesis
studies confirm that the interface observed in the crystal structure is relevant
for signaling. The asymmetric binding mode of Spz to Toll is similar to that of
nerve growth factor (NGF) in complex with the p75 neurotrophin receptor but is
distinct from that of microbial ligands bound to the Toll-like receptors.
Overall, this study indicates an allosteric signaling mechanism for Toll in
which ligand binding to the N terminus induces a conformational change that
couples to homodimerization of juxtamembrane structures in the Toll ectodomain C
terminus.
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