Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit

Nature. 1994 Mar 3;368(6466):67-70. doi: 10.1038/368067a0.


The beta-subunit is an integral component of purified voltage-sensitive Ca2+ channels. Modulation of Ca2+ channel activity by the beta-subunit, which includes significant increases in transmembrane current and/or changes in kinetics, is observed on coexpression of six alpha 1-subunit genes with four beta-subunit genes in all alpha 1-beta combinations tested. Recent reports suggest that this regulation is not due to targeting of the alpha 1-subunit to the plasma membrane but is probably a result of a conformational change induced by the beta-subunit. Here we report that the beta-subunit binds to the cytoplasmic linker between repeats I and II of the dihydropyridine-sensitive alpha 1-subunits from skeletal (alpha 1S) and cardiac muscles (alpha 1C-a), and also with the more distantly related neuronal alpha 1A and omega-conotoxin GVIA-sensitive alpha 1B-subunits. Sequence analysis of the beta-subunit binding site identifies a conserved motif (QQ-E--L-GY--WI--E) positioned 24 amino acids from the IS6 transmembrane domain in each alpha 1-subunit. Mutations within this motif reduce the stimulation of peak currents by the beta-subunit and alter inactivation kinetics and voltage-dependence of activation. Conservation of the beta-subunit binding motif in these functionally distinct calcium channels suggests a critical role for the I-II cytoplasmic linker of the alpha 1-subunit in channel modulation by the beta-subunit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Calcium Channels / chemistry
  • Calcium Channels / immunology
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type
  • Cloning, Molecular
  • Cytoplasm / metabolism
  • Dihydropyridines / pharmacology
  • Epitopes
  • Molecular Sequence Data
  • Muscle Proteins / chemistry
  • Muscle Proteins / metabolism
  • Peptides / pharmacology
  • Rabbits
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Sequence Analysis
  • omega-Conotoxin GVIA


  • Calcium Channels
  • Calcium Channels, L-Type
  • Dihydropyridines
  • Epitopes
  • Muscle Proteins
  • Peptides
  • Recombinant Fusion Proteins
  • 1,4-dihydropyridine
  • omega-Conotoxin GVIA