RGD Reference Report - The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. - Rat Genome Database

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The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.

Authors: Lishko, PV  Procko, E  Jin, X  Phelps, CB  Gaudet, R 
Citation: Lishko PV, etal., Neuron. 2007 Jun 21;54(6):905-18.
RGD ID: 8553505
Pubmed: PMID:17582331   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuron.2007.05.027   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
calcium ion transmembrane transport involved_inIMP 8553505PMID:17582331UniProt 
cellular response to alkaloid involved_inIMP 8553505PMID:17582331UniProt 
cellular response to ATP involved_inIDA 8553505PMID:17582331UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
plasma membrane located_inIMP 8553505PMID:17582331UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Trpv1  (transient receptor potential cation channel, subfamily V, member 1)


Additional Information