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 |
Journal | Science |
Volume | 355 |
Issue | 6328 |
Date Published | 2017 03 03 |
ISSN | 1095-9203 |
Keywords | Animals, Conserved Sequence, Cryoelectron Microscopy, Glycosylation, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits, Models, Chemical, Periplaneta, Protein Domains, Voltage-Gated Sodium Channels |
Abstract | <p>Voltage-gated sodium (Na) 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 Na channel from American cockroach (designated NaPaS) 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 VSD, and a carboxy-terminal domain binds to the III-IV linker. The structure of NaPaS establishes an important foundation for understanding function and disease mechanism of Na and related voltage-gated calcium channels.</p> |
DOI | 10.1126/science.aal4326 |
Alternate Journal | Science |
PubMed ID | 28183995 |