Referenced in: none

Automatically associated channels: Cav1.2

Title: Apo calmodulin binding to the L-type voltage-gated calcium channel Cav1.2 IQ peptide.

Authors: Lu-Yun Lian, Daniel Myatt, Ashraf Kitmitto

Journal, date & volume: Biochem. Biophys. Res. Commun., 2007 Feb 16 , 353, 565-70

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17189613

Abstract
The influx of calcium through the L-type voltage-gated calcium channels (LTCCs) is the trigger for the process of calcium-induced calcium release (CICR) from the sarcoplasmic reticulum, an essential step for cardiac contraction. There are two feedback mechanisms that regulate LTCC activity: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF), both of which are mediated by calmodulin (CaM) binding. The IQ domain (aa 1645-1668) housed within the cytoplasmic domain of the LTCC Cav1.2 subunit has been shown to bind both calcium-loaded (Ca2+CaM ) and calcium-free CaM (apoCaM). Here, we provide new data for the structural basis for the interaction of apoCaM with the IQ peptide using NMR, revealing that the apoCaM C-lobe residues are most significantly perturbed upon complex formation. In addition, we have employed transmission electron microscopy of purified LTCC complexes which shows that both apoCaM and Ca2+CaM can bind to the intact channel.