Structure-guided unlocking of Na_X reveals a non-selective tetrodotoxin-sensitive cation channel.

ABSTRACT: Unlike classical voltage-gated sodium (Na_V) channels, Na_X has been characterized as a voltage-insensitive, tetrodotoxin-resistant, sodium (Na⁺)-activated channel involved in regulating Na⁺ homeostasis. However, Na_X remains refractory to functional characterization in traditional heterologous systems. Here, to gain insight into its atypical physiology, we determine structures of the human Na_X channel in complex with the auxiliary β3-subunit. Na_X reveals structural alterations within the selectivity filter, voltage sensor-like domains, and pore module. We do not identify an extracellular Na⁺-sensor or any evidence for a Na⁺-based activation mechanism in Na_X. Instead, the S6-gate rema

SUBMITTER: Noland CL 

PROVIDER: S-EPMC8931054 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature