|Title||Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Shen, H, Zhou, Q, Pan, X, Li, Z, Wu, J, Yan, N|
|Date Published||2017 03 03|
|Keywords||Animals, Conserved Sequence, Cryoelectron Microscopy, Glycosylation, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits, Models, Chemical, Periplaneta, Protein Domains, Voltage-Gated Sodium Channels|
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 Nav channel 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 Nav and related voltage-gated calcium channels.