Journal article
Calcium channel β-subunit binds to a conserved motif in the I–II cytoplasmic linker of the α1-subunit
Nature (London), Vol.368(6466), pp.67-70
03/1994
DOI: 10.1038/368067a0
PMID: 7509046
Abstract
THE β-subunit is an integral component of purified voltage-sensitive Ca2+ channels1–3. Modulation of Ca2+ channel activity by the β-subunit, which includes significant increases in transmembrane current and/or changes in kinetics, is observed on coexpression of six α1-subunit genes with four β-subunit genes in all α1- β combinations tested4–12. Recent reports suggest that this regulation is not due to targeting of the α1-subunit to the plasma membrane but is probably a result of a conformational change induced by the β-subunit11,13. Here we report that the β-subunit binds to the cytoplasmic linker between repeats I and II of the dihydropyridine-sensitive α1-subunits from skeletal (α1S) and cardiac muscles (α1C-a), and also with the more distantly related neuronal α1A and ω-conotoxin GVIA-sensitive aα1B-subunits. Sequence analysis of the β-subunit binding site identifies a conserved motif (QQ-E--L-GY--WI---E) positioned 24 amino acids from the IS6 transmem-brane domain in each α1-subunit. Mutations within this motif reduce the stimulation of peak currents by the β-subunit and alter inactivation kinetics and voltage-dependence of activation. Conser-vation of the β-subunit binding motif in these functionally distinct calcium channels suggests a critical role for the I-II cytoplasmic linker of the α1-subunit in channel modulation by the β-subunit.
Details
- Title: Subtitle
- Calcium channel β-subunit binds to a conserved motif in the I–II cytoplasmic linker of the α1-subunit
- Creators
- Marion PragnellMichel De WaardYasuo MoriTsutomu TanabeTerry P SnutchKevin P Campbell
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.368(6466), pp.67-70
- DOI
- 10.1038/368067a0
- PMID
- 7509046
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 03/1994
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020846702771
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