3D Structure of the Skeletal Muscle Dihydropyridine Receptor

The dihydropyridine receptors (DHPR) are L-type voltage-gated calcium channels that regulate the flux of calcium ions across the cell membrane. Here we present the three-dimensional (3D) structure at ∼27 A˚ resolution of purified skeletal muscle DHPR, as determined by electron microscopy and single particle analysis. Here both biochemical and 3D structural data indicate that DHPR is dimeric. DHPR dimers are composed of two arch-shaped monomers ∼210 A˚ across and ∼75 A˚ thick, that interact very tightly at each end of the arch. The roughly toroidal structure of the two monomers encloses a cylindrical space of ∼80 A˚ diameter, which is then closed on each side by two dome-shaped protein densities reaching over from each monomer arch. The dome-shaped domains have a length of ∼80–90 A˚ and a maximum height of ∼45 A˚. Small orifices punctuate their exterior surface. The 3D structure disclosed here may have important implications for the understanding of DHPR Ca2+ channel function. We also propose a model for its in vivo interactions with the calcium release channel at the junctional sarcoplasmic recticulum. [Copyright &y& Elsevier]