Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex

Yunlu Kang, Jing-Xiang Wu and Lei Chen ()
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Yunlu Kang: Peking University
Jing-Xiang Wu: Peking University
Lei Chen: Peking University

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-20002-9

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