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Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange
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Abstract
Members of the SLC26 family constitute a conserved class of anion transport proteins, which encompasses uncoupled transporters with channel-like properties, coupled exchangers and motor proteins. Among the 10 functional paralogs in humans, several participate in the secretion of bicarbonate in exchange with chloride and thus play an important role in maintaining pH homeostasis. Previously, we have elucidated the structure of murine SLC26A9 and defined its function as an uncoupled chloride transporter (Walter et al., 2019). Here we have determined the structure of the closely related human transporter SLC26A6 and characterized it as a coupled exchanger of chloride with bicarbonate and presumably also oxalate. The structure defines an inward-facing conformation of the protein that generally resembles known structures of SLC26A9. The altered anion selectivity between both paralogs is a consequence of a remodeled ion binding site located in the center of a mobile unit of the membrane-inserted domain, which also accounts for differences in the coupling mechanism.
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Self-citation
Metadata
- Authors
- Tippett, D. N., Breen, C., Butler, S. J., Sawicka, M., & Dutzler, R.
- Affiliations
- University of Zurich (CH)
- Loughborough University (GB)
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-06-23
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W4381735028
- Cited by
- 3
- References
- 47
- Citations by year
- 2024: 3
- FWCI
- 0.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_163421)
- Engineering and Physical Sciences Research Council (EP/S032339/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- SLC26A6, SLC26 family, anion exchanger, chloride transport, bicarbonate secretion, oxalate transport, protein structure, anion selectivity, pH homeostasis, SLC26A9, inward-facing conformation
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