Comparative structural analysis of human Na_v1.1 and Na_v1.5 reveals mutational hotspots for sodium channelopathies.

ABSTRACT: Among the nine subtypes of human voltage-gated sodium (Na_v) channels, the brain and cardiac isoforms, Na_v1.1 and Na_v1.5, each carry more than 400 missense mutations respectively associated with epilepsy and cardiac disorders. High-resolution structures are required for structure-function relationship dissection of the disease variants. We report the cryo-EM structures of the full-length human Na_v1.1-β4 complex at 3.3 Å resolution here and the Na_v1.5-E1784K variant in the accompanying paper. Up to 341 and 261 disease-related missense mutations in Na_v1.1 and Na_v1.5, respectively, are resolved. Comparative structural analysis reveals several clusters of disease mutations that are common to both Na_v1.1 and

SUBMITTER: Pan X 

PROVIDER: S-EPMC7980448 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature