Solution structure of the N‐terminal A domain of the human voltage‐gated Ca 2+ channel β 4a subunit

Abstract

Ca 2+ channel β subunits regulate trafficking and gating (opening and closing) of voltage‐dependent Ca 2+ channel α 1 subunits. Based on primary sequence comparisons, they are thought to be modular structures composed of five domains (A–E) that are related to the large family of membrane associated guanylate‐kinase (MAGUK) proteins. The crystal structures of the β subunit core, B–D, domains have recently been reported; however, very little is known about the structures of the A and E domains. The N‐terminal A domain is a hypervariable region that differs among the four subtypes of Ca 2+ channel β subunits (β 1 –β 4 ). Furthermore, this domain undergoes alternative splicing to create multiple N‐terminal structures within a given gene class that have distinct effects on gating. We have solved the solution structure of the A domain of the human β 4a subunit, a splice variant that we have shown previously to have α 1 subunit subtype‐specific effects on Ca 2+ channel trafficking and gating.