ArticleThe Journal of biological chemistry2008
Sequence differences in the IQ motifs of CaV1.1 and CaV1.2 strongly impact calmodulin binding and calcium-dependent inactivation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Calmodulin Mutations in Human Disease.Channels (Austin, Tex.) · 2023Review
- The mechanism of complex formation between calmodulin and voltage gated calcium channels revealed by molecular dynamics.PloS one · 2021Article
- Role of defective CaJournal of cell communication and signaling · 2018Review
- Stac Proteins Suppress CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Duplex signaling by CaM and Stac3 enhances CaThe Journal of general physiology · 2018Article
- Bilobal architecture is a requirement for calmodulin signaling to CaProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Calmodulin limits pathogenic Na+ channel persistent current.The Journal of general physiology · 2017Article
- A novel calmodulin site in the Cav1.2 N-terminus regulates calcium-dependent inactivation.Pflugers Archiv : European journal of physiology · 2014Article
- Ca(V)1.1: The atypical prototypical voltage-gated Ca²⁺ channel.Biochimica et biophysica acta · 2013Review
- Ca2+-dependent modulation of voltage-gated Ca2+ channels.Biochimica et biophysica acta · 2012Review
- Voltage clamp methods for the study of membrane currents and SR Ca(2+) release in adult skeletal muscle fibres.Progress in biophysics and molecular biology · 2012Review
- Thermodynamic linkage between calmodulin domains binding calcium and contiguous sites in the C-terminal tail of Ca(V)1.2.Biophysical chemistry · 2011Article
- Ryanodine receptors: structure, expression, molecular details, and function in calcium release.Cold Spring Harbor perspectives in biology · 2010Review
- Cooperative regulation of Ca(v)1.2 channels by intracellular Mg(2+), the proximal C-terminal EF-hand, and the distal C-terminal domain.The Journal of general physiology · 2009Article
- Determinants in CaV1 channels that regulate the Ca2+ sensitivity of bound calmodulin.The Journal of biological chemistry · 2009Article
- Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.Channels (Austin, Tex.)Review
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5 authors.
Funding
Abstract
The proximal C terminus of the cardiac L-type calcium channel (Ca(V)1.2) contains structural elements important for the binding of calmodulin (CaM) and calcium-dependent inactivation, and exhibits extensive sequence conservation with the corresponding region of the skeletal L-type channel (Ca(V)1.1). However, there are several Ca(V)1.1 residues that are both identical in six species and are non-conservatively changed from the corresponding Ca(V)1.2 residues, including three of the "IQ motif." To investigate the functional significance of these residue differences, we used native gel electrophoresis and expression in intact myotubes to compare the binding of CaM to extended regions (up to 300 residues) of the C termini of Ca(V)1.1 and Ca(V)1.2. We found that in the presence of Ca(2+) (either millimolar or that in resting myotubes), CaM bound strongly to C termini of Ca(V)1.2 but not of Ca(V)1.1. Furthermore, replacement of two residues (Tyr(1657) and Lys(1662)) within the IQ motif of a C-terminal Ca(V)1.2 construct with the divergent residues of Ca(V)1.1 (His(1532) and Met(1537)) led to a weakening of CaM binding (native gels), whereas the reciprocal substitution in Ca(V)1.1 caused a gain of CaM binding. In full-length Ca(V)1.2, substitution of these same two divergent residues with those of Ca(V)1.1 (Y1657H, K1662M) eliminated calcium-dependent inactivation of the heterologously expressed channel. Thus, our results reveal that a conserved difference between the IQ motifs of Ca(V)1.2 and Ca(V)1.1 has a profound effect on both CaM binding and calcium-dependent inactivation.
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