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

Sci Rep. 2015 Feb 10:5:8370. doi: 10.1038/srep08370.

Abstract

Dihydropyridine receptor (DHPR), an L-type Ca(2+) 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-Å resolution cryo-electron microscopy structure of the skeletal DHPR/L-type Ca(2+) 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 α1 and α2 subunits are located in the "trapezoid" and the β subunit is located in the "tetrahedroid". This structure revealed the molecular architecture of a eukaryotic Ca(2+) channel complex. Furthermore, this structure provides structural insights into the key elements of DHPR involved in physical coupling with the RyR/Ca(2+) release channel and shed light onto the mechanism of excitation-contraction coupling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, L-Type / chemistry*
  • Calcium Channels, L-Type / metabolism
  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Cryoelectron Microscopy
  • Muscle Proteins / chemistry*
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / chemistry*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / ultrastructure
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Rabbits
  • Ryanodine Receptor Calcium Release Channel / chemistry*
  • Ryanodine Receptor Calcium Release Channel / metabolism

Substances

  • Calcium Channels, L-Type
  • Muscle Proteins
  • Protein Subunits
  • Ryanodine Receptor Calcium Release Channel