Structure of the human sodium leak channel NALCN in complex with FAM155A.

ABSTRACT: NALCN, a sodium leak channel expressed mainly in the central nervous system, is responsible for the resting Na⁺ permeability that controls neuronal excitability. Dysfunctions of the NALCN channelosome, NALCN with several auxiliary subunits, are associated with a variety of human diseases. Here, we report the cryo-EM structure of human NALCN in complex with FAM155A at an overall resolution of 3.1 angstroms. FAM155A forms extensive interactions with the extracellular loops of NALCN that may help stabilize NALCN in the membrane. A Na⁺ ion-binding site, reminiscent of a Ca²⁺ binding site in Ca_v channels, is identified in the unique EEKE selectivity filter. Despite its 'leaky' nature, the channel is closed and the intracellular gate is sealed by S6

SUBMITTER: Xie J 

PROVIDER: S-EPMC7672056 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature