5gjv | pdb_00005gjv
Structure of the mammalian voltage-gated calcium channel Cav1.1 complex at near atomic resolution
Structural highlights
Function[CCG1_RABIT] This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex. [CAC1S_RABIT] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle. [CA2D1_RABIT] The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling. Publication Abstract from PubMedThe voltage-gated calcium (Cav) channels convert membrane electrical signals to intracellular Ca2+-mediated events. Among the ten subtypes of Cav channel in mammals, Cav1.1 is specified for the excitation-contraction coupling of skeletal muscles. Here we present the cryo-electron microscopy structure of the rabbit Cav1.1 complex at a nominal resolution of 3.6 A. The inner gate of the ion-conducting alpha1-subunit is closed and all four voltage-sensing domains adopt an 'up' conformation, suggesting a potentially inactivated state. The extended extracellular loops of the pore domain, which are stabilized by multiple disulfide bonds, form a windowed dome above the selectivity filter. One side of the dome provides the docking site for the alpha2delta-1-subunit, while the other side may attract cations through its negative surface potential. The intracellular I-II and III-IV linker helices interact with the beta1a-subunit and the carboxy-terminal domain of alpha1, respectively. Classification of the particles yielded two additional reconstructions that reveal pronounced displacement of beta1a and adjacent elements in alpha1. The atomic model of the Cav1.1 complex establishes a foundation for mechanistic understanding of excitation-contraction coupling and provides a three-dimensional template for molecular interpretations of the functions and disease mechanisms of Cav and Nav channels. Structure of the voltage-gated calcium channel Cav1.1 at 3.6 A resolution.,Wu J, Yan Z, Li Z, Qian X, Lu S, Dong M, Zhou Q, Yan N Nature. 2016 Aug 31;537(7619):191-196. doi: 10.1038/nature19321. PMID:27580036[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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