The molecular architecture of dihydropyrindine receptor/L-type Ca2+ channel complex

Dihydropyridine receptor (DHPR), an L-type Ca2+ channel complex, plays an essential role in muscle contraction, secretion, integration of synaptic input in neurons and synaptic transmission. The molecular architecture of DHPR complex remains elusive. Here we present a 15-angstrom resolution cryo-electron microscopy structure of the skeletal DHPR/L-type Ca2+ channel complex. The DHPR has an asymmetrical main body joined by a hook-like extension. The main body is composed of a trapezoid and a tetrahedroid. Homologous crystal structure docking and site-specific antibody labelling revealed that the alpha 1 and alpha 2 subunits are located in the trapezoid and the beta subunit is located in the tetrahedroid. This structure revealed the molecular architecture of a eukaryotic Ca2+ channel complex. Furthermore, this structure provides structural insights into the key elements of DHPR involved in physical coupling with the RyR/Ca2+ release channel and shed light onto the mechanism of excitation-contraction coupling.