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PDBsum entry 2nyj
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Transport protein
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PDB id
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2nyj
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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 ankyrin repeats of trpv1 bind multiple ligands and modulate channel sensitivity.
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Authors
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P.V.Lishko,
E.Procko,
X.Jin,
C.B.Phelps,
R.Gaudet.
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Ref.
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Neuron, 2007,
54,
905-918.
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PubMed id
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Abstract
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TRPV1 plays a key role in nociception, as it is activated by heat, low pH, and
ligands such as capsaicin, leading to a burning pain sensation. We describe the
structure of the cytosolic ankyrin repeat domain (ARD) of TRPV1 and identify a
multiligand-binding site important in regulating channel sensitivity within the
TRPV1-ARD. The structure reveals a binding site that accommodates triphosphate
nucleotides such as ATP, and biochemical studies demonstrate that calmodulin
binds the same site. Electrophysiology experiments show that either ATP or PIP2
prevent desensitization to repeated applications of capsaicin, i.e.,
tachyphylaxis, while calmodulin plays an opposing role and is necessary for
tachyphylaxis. Mutations in the TRPV1-ARD binding site eliminate tachyphylaxis.
We present a model for the calcium-dependent regulation of TRPV1 via competitive
interactions of ATP and calmodulin at the TRPV1-ARD-binding site and discuss its
relationship to the C-terminal region previously implicated in interactions with
PIP2 and calmodulin.
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