Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33273469.
- Also identified by DOI 10.1038/s41467-020-20002-9 and PMC identifier 7712781.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Resting membrane potential determines the excitability of the cell and is essential for the cellular electrical activities. The NALCN channel mediates sodium leak currents, which positively adjust resting membrane potential towards depolarization. The NALCN channel is involved in several neurological processes and has been implicated in a spectrum of neurodevelopmental diseases. Here, we report the cryo-EM structure of rat NALCN and mouse FAM155A complex to 2.7 Å resolution. The structure reveals detailed interactions between NALCN and the extracellular cysteine-rich domain of FAM155A. We find that the non-canonical architecture of NALCN selectivity filter dictates its sodium selectivity and calcium block, and that the asymmetric arrangement of two functional voltage sensors confers the modulation by membrane potential. Moreover, mutations associated with human diseases map to the domain-domain interfaces or the pore domain of NALCN, intuitively suggesting their pathological mechanisms.
Medical subject headings
- Calcium Channels
- Ion Channels
- Membrane Proteins
- Sodium