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 recticulum, 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. © 2006 Elsevier Inc. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 565-570 |
| Number of pages | 5 |
| Journal | Biochemical and biophysical research communications |
| Volume | 353 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 16 Feb 2007 |
Keywords
- Apocalmodulin
- Electron microscopy
- L-type voltage-gated calcium channels
- NMR
- Protein-protein interactions