title: Ca(2+) binding protein S100A1 competes with calmodulin and PIP2 for binding site on the C-terminus of the TPRV1 receptor.
abstract: Transient receptor potential vanilloid 1 ion channel (TRPV1) belongs to the TRP family of ion channels. These channels play a role in many important biological processes such as thermosensation and pain transduction. The TRPV1 channel was reported to be also involved in nociception. Ca(2+) ions are described to participate in the regulation of TRP channels through the interaction with Ca(2+)-binding proteins, such as calmodulin or S100A1. Calmodulin is involved in the Ca(2+)-dependent regulation of TRPV1 via its binding to the TRPV1 C-terminal region. However, the role of the Ca(2+)-binding protein S100A1 in the process of TRP channel regulation remains elusive. Here we characterized a region on the TRPV1 C-terminus responsible for the interaction with S100A1 using biochemical and biophysical tools. We found that this region overlaps with previously identified calmodulin and PIP2 binding sites and that S100A1 competes with calmodulin and PIP2 for this binding site. We identified several positively charged residues within this region, which have crucial impact on S100A1 binding, and we show that the reported S100A1-TRPV1 interaction is calcium-dependent. Taken together, our data suggest a mechanism for the mutual regulation of PIP2 and the Ca(2+)-binding proteins S100A1 and calmodulin to TRPV1.
authors.forename: Lenka
authors.initials: L
authors.lastname: Grycova
authors.forename: Blanka
authors.initials: B
authors.lastname: Holendova
authors.affiliation: ∥B CUBE - Center for Molecular Bioengineering, Technische Universität Dresden, Arnoldstrasse 18, 01307 Dresden, Germany.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Lansky
authors.forename: Ladislav
authors.initials: L
authors.lastname: Bumba
authors.forename: Michaela
authors.initials: M
authors.lastname: Jirku
authors.forename: Kristyna
authors.initials: K
authors.lastname: Bousova
authors.forename: Jan
authors.initials: J
authors.lastname: Teisinger
mesh_terms: D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena / Q000235:genetics; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005454:Fluorescence Polarization; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D016296:Mutagenesis; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D017354:Point Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D017434:Protein Structure, Tertiary; D051381:Rats; D009418:S100 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D020349:Surface Plasmon Resonance; D050916:TRPV Cation Channels / Q000737:chemistry / Q000378:metabolism*; D013879:Thioredoxins / Q000494:pharmacology
chemical_list: D002147:Calmodulin; D046912:Multiprotein Complexes; D019269:Phosphatidylinositol 4,5-Diphosphate; D009418:S100 Proteins; C110294:S100A1 protein; D050916:TRPV Cation Channels; D013879:Thioredoxins; D002118:Calcium
keywords: S100A1; TRPV1; calcium binding protein; calmodulin; fluorescence anisotropy; surface plasmon resonance; vanilloid receptor