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Chen Lei's research group reports the structural mechanism of UNC79-UNC80 regulating the sodium channel NALCN-FAM155A

 Last Update: 2022-08-11
 Source: Internet
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The Resting Membrane Potential (RMP) of nerve cells affects the excitability of nerve cells and is essential for maintaining the normal physiological functions of nerve cel.

On May 12, 2022, the research group of Chen Lei, Institute of Molecular Medicine, School of Future Technology, Peking University, Peking University-Tsinghua Life Science Joint Center, and National Center for Biomedical Imaging reported the freezing of NALCN-FAM155A-UNC79-UNC80 complex in the journal Nature Communications Electron microscopy structure and mechanism of UNC79-UNC80 regulation of NALCN-FAM155.

In 2020, Chen Lei's group reported the high-resolution structure of the NALCN-FAM155A subcomplex ¹² , elucidating the structural basis of NALCN's sodium ion selectivity, extracellular calcium ion blocking, and voltage regulation properties, and found that in NALCN channels The unique CIH helix on the II-III linker binds to the C.

Figure 1: Structure of the NALCN-FAM155A-UNC79-UNC80 complex

The authors then studied how UNC79 and UNC80 regulate NALCN activity based on this structure, and found that three accessory subunits of UNC79, UNC80 and FAM155A are essential for the correct transport of NALCN to the cell membra.

Figure 2: Schematic representation of the mechanism by which UNC79-UNC80 activates NALCN

Unlike UNIM-A and UNIM-B, when UNIM-C was mutated to disrupt the interaction of UNIM-C with UNC79/80, the upper membrane of NALCN and the magnitude of sodium leakage current were not affected, but NALCN was more difficult Activated by voltage, the conductance-voltage curve (GV curve) shifted significantly to the rig.

The study was published on BioRxiv ( https://d.

The first author of this study is Kang Yunlu, a postdoctoral fellow in Chen Lei's group, and Chen Lei is the second and corresponding auth.

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