The voltage-dependent calcium channel β subunit contains two stable interacting domains

Voltage-dependent calcium channels selectively enable Ca2+ ion movement through cellular membranes. These multiprotein complexes are involved in a wide spectrum of biological processes such as signal transduction and cellular homeostasis. alpha(1) is the membrane pore-forming subunit, whereas beta is an intracellular subunit that binds to alpha(1), facilitating and modulating channel function. We have expressed, purified, and characterized recombinant beta(3) and beta(2a) using both biochemical and biophysical methods, including electrophysiology, to better understand the beta family's protein structural and functional correlates. Our results indicate that the beta protein is composed of two distinct domains that associate with one another in a stable manner. The data also suggest that the polypeptide regions outside these domains are not structured when beta is not in complex with the channel. In addition, the beta structural core, comprised of just these two domains without other sequences, binds tightly to the alpha interaction domain (AID) motif, a sequence derived from the alpha(1) subunit and the principal anchor site of beta. Domain II is responsible for this binding, but domain I enhances it.