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Publication Abstract from PubMed

The bestrophin family of calcium (Ca(2+))-activated chloride (Cl(-)) channels, which mediate the influx and efflux of monovalent anions in response to the levels of intracellular Ca(2+), comprises four members in mammals (bestrophin 1-4). Here we report cryo-EM structures of bovine bestrophin-2 (bBest2) bound and unbound by Ca(2+) at 2.4- and 2.2-A resolution, respectively. The bBest2 structure highlights four previously underappreciated pore-lining residues specifically conserved in Best2 but not in Best1, illustrating the differences between these paralogs. Structure-inspired electrophysiological analysis reveals that, although the channel is sensitive to Ca(2+), it has substantial Ca(2+)-independent activity for Cl(-), reflecting the opening at the cytoplasmic restriction of the ion conducting pathway even when Ca(2+) is absent. Moreover, the ion selectivity of bBest2 is controlled by multiple residues, including those involved in gating.

Structural and functional characterization of the bestrophin-2 anion channel.,Owji AP, Zhao Q, Ji C, Kittredge A, Hopiavuori A, Fu Z, Ward N, Clarke OB, Shen Y, Zhang Y, Hendrickson WA, Yang T Nat Struct Mol Biol. 2020 Apr;27(4):382-391. doi: 10.1038/s41594-020-0402-z. Epub, 2020 Apr 6. PMID:32251414^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.