7CU3

Structure of mammalian NALCN-FAM155A complex at 2.65 angstrom

Summary for 7CU3

• Entry DOI: 10.2210/pdb7cu3/pdb
• EMDB information: 30470
• Descriptor: Sodium leak channel non-selective protein, Transmembrane protein FAM155A, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: nalcn, channel, fam155, nca, nlf, transport protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 2
• Total formula weight: 263530.72

Authors

Chen, L.,Kang, Y. (deposition date: 2020-08-20, release date: 2020-11-18, Last modification date: 2025-07-02)

Primary citation

Kang, Y.,Wu, J.X.,Chen, L.
Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex.
Nat Commun, 11:6199-6199, 2020

PubMed 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.

PubMed: 33273469
DOI: 10.1038/s41467-020-20002-9

Experimental method

ELECTRON MICROSCOPY (2.65 Å)