title: Insights into the roles of conserved and divergent residues in the ankyrin repeats of TRPV ion channels.
abstract: Ion channels are often modulated by intracellular calcium levels. TRPV1, a channel responsible for the burning pain sensation in response to heat, acid or capsaicin, is desensitized at high intracellular calcium concentrations. We recently identified a multiligand-binding site in the N-terminal ankyrin repeat domain (ARD) of TRPV1 that binds ATP and sensitizes the channel. Calcium-calmodulin binds the same site and is necessary for calcium-mediated TRPV1 desensitization. Here, we examine in more detail the conservation of this TRPV1 multiligand-binding site in other species. Furthermore, using sequence analysis, we determine that the unusually twisted shape of the TRPV1-ARD is likely conserved in other TRPV channels, but not in the ARDs of other TRP subfamilies.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02318, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Phelps
authors.forename: Erik
authors.initials: E
authors.lastname: Procko
authors.forename: Polina V
authors.initials: PV
authors.lastname: Lishko
authors.forename: Ruiqi R
authors.initials: RR
authors.lastname: Wang
authors.forename: Rachelle
authors.initials: R
authors.lastname: Gaudet
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017089:Ankyrin Repeat; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D017124:Conserved Sequence; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002147:Calmodulin; D008024:Ligands; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D000255:Adenosine Triphosphate; D002118:Calcium