Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution.
Voltage-gated sodium (Nav) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryogenic electron microscopy structure of a putative Navchannel from American cockroach (designated NavPaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops. On the cytoplasmic side, a conserved amino-terminal domain is placed below VSDI, and a carboxy-terminal domain binds to the III-IV linker. The structure of NavPaS establishes an important foundation for understanding function and disease mechanism of Navand related voltage-gated calcium channels.
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.
Huaizong
0000-0002-1216-5393
H
Shen
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.|Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
Qiang
Q
Zhou
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.
Xiaojing
X
Pan
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.|Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
Zhangqiang
0000-0002-3296-2293
Z
Li
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.|Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
Jianping
0000-0001-9869-7691
J
Wu
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. nyan@tsinghua.edu.cn.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.|Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
Nieng
0000-0003-4829-7416
N
Yan
D000818:Animals; D017124:Conserved Sequence; D020285:Cryoelectron Microscopy; D006031:Glycosylation; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000737:chemistry; D008956:Models, Chemical; D010526:Periplaneta; D000072417:Protein Domains; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000648:ultrastructure*
D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D061566:Voltage-Gated Sodium Channels