title: Characterization of the calmodulin-binding site in the N terminus of CaV1.2.
abstract: Interaction of calmodulin (CaM) with the C-terminus (CT) of the L-type Ca(V)1.2 channel is crucial for Ca(2+)-dependent inactivation (CDI). CaM also binds to the N-terminus (NT), and a CaM-formed "bridge" between CT and NT has been proposed to control CDI. We characterized the interaction of CaM with its NT-binding peptide. Binding is Ca(2+)-dependent with an affinity of 0.6 microM. Mutations in NT of Ca(V)1.2 that abolished the binding of CaM only slightly weakened the CDI but also accelerated the VDI. CaM did not foster an interaction between the CaM-binding peptides of NT and CT. Thus, the role of CaM's interaction with the Ca(V)1.2 NT remains to be determined.
authors.affiliation: Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. advabne@post.tau.ac.il
authors.forename: Adva
authors.initials: A
authors.lastname: Benmocha
authors.forename: Lior
authors.initials: L
authors.lastname: Almagor
authors.forename: Shimrit
authors.initials: S
authors.lastname: Oz
authors.forename: Joel A
authors.initials: JA
authors.lastname: Hirsch
authors.forename: Nathan
authors.initials: N
authors.lastname: Dascal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020746:Calcium Channels, L-Type / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005982:Glutathione Transferase; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000166:cytology; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014982:Xenopus laevis
chemical_list: D020746:Calcium Channels, L-Type; D002147:Calmodulin; C419385:L-type calcium channel alpha(1C); D010455:Peptides; D005982:Glutathione Transferase