Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel Na_V1.2.

ABSTRACT: Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel Na_V1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat Na_V1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca²⁺)₄-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca²⁺)₄-CaM, NMR demonstrated that Na_V1.2 IQ motif peptide (Na_V1.2_IQp) exclusively made contacts with C-domain residues of CaM (CaM_C). To understand how calcium triggers conformational change at the CaM-IQ interface, we determined a so

SUBMITTER: Hovey L 

PROVIDER: S-EPMC5503752 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature