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Calcium channel β-subunit binds to a conserved motif in the I–II cytoplasmic linker of the α1-subunit

Nature volume 368, pages 67–70 (1994)Cite this article

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.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Department of Physiology and Biophysics and Program in Neuroscience, University of Iowa College of Medicine, 400 EMRB, Iowa City, Iowa, 52242, USA

    Marion Pragnell, Michel De Waard & Kevin P. Campbell

  2. Department of Medical Chemistry, Kyoto University, Kyoto, 606, Japan

    Yasuo Mori

  3. Howard Hughes Medical Institute, Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, 06536, USA

    Tsutomu Tanabe

  4. Biotechnology Laboratory and Departments of Zoology and Neuroscience, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada

    Terry P. Snutch

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  6. Kevin P. Campbell
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Pragnell, M., De Waard, M., Mori, Y. et al. Calcium channel β-subunit binds to a conserved motif in the I–II cytoplasmic linker of the α1-subunit. Nature 368, 67–70 (1994). https://doi.org/10.1038/368067a0

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