Structural highlights
Function
ASIC5_HUMAN Forms bile acid-gated sodium channels and may play a role in bile acid-dependent absorption and secretion by epithelial cells of the bile ducts (PubMed:10767424, PubMed:22735174). Displays high selectivity for sodium ions but can also permit the permeation of other cations (Probable). The gating could be indirect and the consequence of alterations of the membrane environment of the channel by bile acids (By similarity). As a sodium channel of type II unipolar brush cells of the vestibulocerebellum, controlling the electrical activity of these cells, could play a role in motor coordination and balance (By similarity).[UniProtKB:Q9R0W5][UniProtKB:Q9R0Y1][1] [2] [3]
Publication Abstract from PubMed
The bile acid-sensitive ion channel (BASIC) is the least understood member of the mammalian epithelial Na(+) channel/degenerin (ENaC/DEG) superfamily of ion channels, which are involved in a variety of physiological processes. While some members of this superfamily, including BASIC, are inhibited by extracellular Ca(2+) (Ca(2+)(o)), the molecular mechanism underlying Ca(2+) modulation remains unclear. Here, by determining the structure of human BASIC (hBASIC) in the presence and absence of Ca(2+) using single-particle cryo-electron microscopy (cryo-EM), we reveal Ca(2+)-dependent conformational changes in the transmembrane domain and beta-linkers. Electrophysiological experiments further show that a glutamate residue in the extracellular vestibule of the pore underpins the Ca(2+)-binding site, whose occupancy determines the conformation of the pore and therefore ion flow through the channel. These results reveal the molecular principles governing gating of BASIC and its regulation by Ca(2+) ions, demonstrating that Ca(2+) ions modulate BASIC function via changes in protein conformation rather than solely from a pore-block, as proposed for other members of this superfamily.
The bile acid-sensitive ion channel is gated by Ca(2+)-dependent conformational changes in the transmembrane domain.,Freitas MM, Gouaux E Nat Commun. 2025 Jul 22;16(1):6746. doi: 10.1038/s41467-025-62038-9. PMID:40695804[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schaefer L, Sakai H, Mattei M, Lazdunski M, Lingueglia E. Molecular cloning, functional expression and chromosomal localization of an amiloride-sensitive Na(+) channel from human small intestine. FEBS Lett. 2000 Apr 14;471(2-3):205-10. PMID:10767424 doi:10.1016/s0014-5793(00)01403-4
- ↑ Wiemuth D, Sahin H, Falkenburger BH, Lefèvre CM, Wasmuth HE, Gründer S. BASIC--a bile acid-sensitive ion channel highly expressed in bile ducts. FASEB J. 2012 Oct;26(10):4122-30. PMID:22735174 doi:10.1096/fj.12-207043
- ↑ Wiemuth D, Sahin H, Falkenburger BH, Lefèvre CM, Wasmuth HE, Gründer S. BASIC--a bile acid-sensitive ion channel highly expressed in bile ducts. FASEB J. 2012 Oct;26(10):4122-30. PMID:22735174 doi:10.1096/fj.12-207043
- ↑ Freitas MM, Gouaux E. The bile acid-sensitive ion channel is gated by Ca(2+)-dependent conformational changes in the transmembrane domain. Nat Commun. 2025 Jul 22;16(1):6746. PMID:40695804 doi:10.1038/s41467-025-62038-9
