National Institutes of Health/National Eye Institute (NIH/NEI)
F31EY030763
United States
National Institutes of Health/National Eye Institute (NIH/NEI)
EY025290
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM127652
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM107462
United States
Citation
Journal: Nat Struct Mol Biol / Year: 2020 Title: Structural and functional characterization of the bestrophin-2 anion channel. Authors: Aaron P Owji / Qingqing Zhao / Changyi Ji / Alec Kittredge / Austin Hopiavuori / Ziao Fu / Nancy Ward / Oliver B Clarke / Yin Shen / Yu Zhang / Wayne A Hendrickson / Tingting Yang / Abstract: The bestrophin family of calcium (Ca)-activated chloride (Cl) channels, which mediate the influx and efflux of monovalent anions in response to the levels of intracellular Ca, comprises four members ...The bestrophin family of calcium (Ca)-activated chloride (Cl) channels, which mediate the influx and efflux of monovalent anions in response to the levels of intracellular Ca, comprises four members in mammals (bestrophin 1-4). Here we report cryo-EM structures of bovine bestrophin-2 (bBest2) bound and unbound by Ca at 2.4- and 2.2-Å 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, it has substantial Ca-independent activity for Cl, reflecting the opening at the cytoplasmic restriction of the ion conducting pathway even when Ca is absent. Moreover, the ion selectivity of bBest2 is controlled by multiple residues, including those involved in gating.
History
Deposition
Feb 21, 2020
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Header (metadata) release
Mar 11, 2020
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Map release
Apr 8, 2020
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Update
Mar 6, 2024
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Current status
Mar 6, 2024
Processing site: RCSB / Status: Released
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