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Structural and Functional Characterization of the Bestrophin-2 Anion Channel

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 (Best1-4). Here we report cryo-EM structures of bovine Best2 (bBest2) bound and...

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Autores principales: Owji, Aaron P., Zhao, Qingqing, Ji, Changyi, Kittredge, Alec, Hopiavuori, Austin, Fu, Ziao, Ward, Nancy, Clarke, Oliver B., Shen, Yin, Zhang, Yu, Hendrickson, Wayne A., Yang, Tingting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150642/
https://www.ncbi.nlm.nih.gov/pubmed/32251414
http://dx.doi.org/10.1038/s41594-020-0402-z
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author Owji, Aaron P.
Zhao, Qingqing
Ji, Changyi
Kittredge, Alec
Hopiavuori, Austin
Fu, Ziao
Ward, Nancy
Clarke, Oliver B.
Shen, Yin
Zhang, Yu
Hendrickson, Wayne A.
Yang, Tingting
author_facet Owji, Aaron P.
Zhao, Qingqing
Ji, Changyi
Kittredge, Alec
Hopiavuori, Austin
Fu, Ziao
Ward, Nancy
Clarke, Oliver B.
Shen, Yin
Zhang, Yu
Hendrickson, Wayne A.
Yang, Tingting
author_sort Owji, Aaron P.
collection PubMed
description 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 (Best1-4). Here we report cryo-EM structures of bovine Best2 (bBest2) bound and unbound by Ca(2+) at 2.4 Å and 2.2 Å, 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.
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spelling pubmed-71506422020-10-06 Structural and Functional Characterization of the Bestrophin-2 Anion Channel Owji, Aaron P. Zhao, Qingqing Ji, Changyi Kittredge, Alec Hopiavuori, Austin Fu, Ziao Ward, Nancy Clarke, Oliver B. Shen, Yin Zhang, Yu Hendrickson, Wayne A. Yang, Tingting Nat Struct Mol Biol Article 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 (Best1-4). Here we report cryo-EM structures of bovine Best2 (bBest2) bound and unbound by Ca(2+) at 2.4 Å and 2.2 Å, 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. 2020-04-06 2020-04 /pmc/articles/PMC7150642/ /pubmed/32251414 http://dx.doi.org/10.1038/s41594-020-0402-z Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Owji, Aaron P.
Zhao, Qingqing
Ji, Changyi
Kittredge, Alec
Hopiavuori, Austin
Fu, Ziao
Ward, Nancy
Clarke, Oliver B.
Shen, Yin
Zhang, Yu
Hendrickson, Wayne A.
Yang, Tingting
Structural and Functional Characterization of the Bestrophin-2 Anion Channel
title Structural and Functional Characterization of the Bestrophin-2 Anion Channel
title_full Structural and Functional Characterization of the Bestrophin-2 Anion Channel
title_fullStr Structural and Functional Characterization of the Bestrophin-2 Anion Channel
title_full_unstemmed Structural and Functional Characterization of the Bestrophin-2 Anion Channel
title_short Structural and Functional Characterization of the Bestrophin-2 Anion Channel
title_sort structural and functional characterization of the bestrophin-2 anion channel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150642/
https://www.ncbi.nlm.nih.gov/pubmed/32251414
http://dx.doi.org/10.1038/s41594-020-0402-z
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