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TitleStructure of the voltage-gated calcium channel Ca(v)1.1 at 3.6 Å resolution.
Journal, issue, pagesNature, Vol. 537, Issue 7619, Page 191-196, Year 2016
Publish dateSep 8, 2016
AuthorsJianping Wu / Zhen Yan / Zhangqiang Li / Xingyang Qian / Shan Lu / Mengqiu Dong / Qiang Zhou / Nieng Yan /
PubMed AbstractThe voltage-gated calcium (Ca) channels convert membrane electrical signals to intracellular Ca-mediated events. Among the ten subtypes of Ca channel in mammals, Ca1.1 is specified for the excitation- ...The voltage-gated calcium (Ca) channels convert membrane electrical signals to intracellular Ca-mediated events. Among the ten subtypes of Ca channel in mammals, Ca1.1 is specified for the excitation-contraction coupling of skeletal muscles. Here we present the cryo-electron microscopy structure of the rabbit Ca1.1 complex at a nominal resolution of 3.6 Å. The inner gate of the ion-conducting α1-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 α2δ-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 β-subunit and the carboxy-terminal domain of α1, respectively. Classification of the particles yielded two additional reconstructions that reveal pronounced displacement of β and adjacent elements in α1. The atomic model of the Ca1.1 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 Ca and Na channels.
External linksNature / PubMed:27580036
MethodsEM (single particle)
Resolution3.6 - 3.9 Å
Structure data

EMDB-9513: Cryo-EM map of the rabbit voltage-gated calcium channel Cav1.1 at 3.6 angstrom resolution
PDB-5gjv: Structure of the mammalian voltage-gated calcium channel Cav1.1 complex at near atomic resolution
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-9514:
ClassIa map of the rabbit voltage-gated calcium channel Cav1.1
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-9515: ClassII map of the rabbit voltage-gated calcium channel Cav1.1
PDB-5gjw: Structure of the mammalian voltage-gated calcium channel Cav1.1 complex for ClassII map
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

ChemComp-CA:
Unknown entry

Source
  • oryctolagus cuniculus (rabbit)
KeywordsMEMBRANE PROTEIN / complex / channel

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