7CM3

Cryo-EM structure of human NALCN in complex with FAM155A

Summary for 7CM3

• Entry DOI: 10.2210/pdb7cm3/pdb
• EMDB information: 30400
• Descriptor: Sodium leak channel non-selective protein, Transmembrane protein FAM155A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: ion channel, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 267576.20

Authors

Wu, J.,Yan, Z.,Ke, M. (deposition date: 2020-07-24, release date: 2020-11-11, Last modification date: 2025-07-02)

Primary citation

Xie, J.,Ke, M.,Xu, L.,Lin, S.,Huang, J.,Zhang, J.,Yang, F.,Wu, J.,Yan, Z.
Structure of the human sodium leak channel NALCN in complex with FAM155A.
Nat Commun, 11:5831-5831, 2020

PubMed 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 Ca binding site in Ca 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, II-III linker and III-IV linker. Our study establishes the molecular basis of Na permeation and voltage sensitivity, and provides important clues to the mechanistic understanding of NALCN regulation and NALCN channelosome-related diseases.

PubMed: 33203861
DOI: 10.1038/s41467-020-19667-z

Experimental method

ELECTRON MICROSCOPY (3.1 Å)