title: Apo calmodulin binding to the L-type voltage-gated calcium channel Cav1.2 IQ peptide.
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.
authors.affiliation: School of Biological Sciences, The University of Liverpool, P.O. Box 147, Liverpool L69 7ZB, UK. lu-yun.lian@liverpool.ac.uk
authors.forename: Lu-Yun
authors.initials: LY
authors.lastname: Lian
authors.forename: Daniel
authors.initials: D
authors.lastname: Myatt
authors.forename: Ashraf
authors.initials: A
authors.lastname: Kitmitto
mesh_terms: D001059:Apoproteins / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D008854:Microscopy, Electron; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D001059:Apoproteins; D020746:Calcium Channels, L-Type; D002147:Calmodulin; C419385:L-type calcium channel alpha(1C)