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

• Published in: Scientific reports 2015-02, Vol.5 (1), p.8370-8370, Article 8370
• Main Authors: Hu, Hongli, Wang, Zhao, Wei, Risheng, Fan, Guizhen, Wang, Qiongling, Zhang, Kaiming, Yin, Chang-Cheng
• Format: Article
• Language: English
• Subjects: 147/28; 631/535; 631/535/1258/1259; Animals; Calcium channels (L-type); Calcium Channels, L-Type - chemistry; Calcium Channels, L-Type - metabolism; Calcium release channels; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cryoelectron Microscopy; Crystal structure; Dihydropyridine; Electron microscopy; Excitation-contraction coupling; Humanities and Social Sciences; Labeling; multidisciplinary; Muscle contraction; 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; Ryanodine receptors; Science; Secretion; Synaptic transmission
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep08370

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.