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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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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. |
format | Online Article Text |
id | pubmed-7150642 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
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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