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- Title
Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE.
- Authors
Wang, Weiguang; Tsirulnikov, Kirill; Zhekova, Hristina R.; Kayık, Gülru; Khan, Hanif Muhammad; Azimov, Rustam; Abuladze, Natalia; Kao, Liyo; Newman, Debbie; Noskov, Sergei Yu.; Zhou, Z. Hong; Pushkin, Alexander; Kurtz, Ira
- Abstract
SLC4 transporters play significant roles in pH regulation and cellular sodium transport. The previously solved structures of the outward facing (OF) conformation for AE1 (SLC4A1) and NBCe1 (SLC4A4) transporters revealed an identical overall fold despite their different transport modes (chloride/bicarbonate exchange versus sodium-carbonate cotransport). However, the exact mechanism determining the different transport modes in the SLC4 family remains unknown. In this work, we report the cryo-EM 3.4 Å structure of the OF conformation of NDCBE (SLC4A8), which shares transport properties with both AE1 and NBCe1 by mediating the electroneutral exchange of sodium-carbonate with chloride. This structure features a fully resolved extracellular loop 3 and well-defined densities corresponding to sodium and carbonate ions in the tentative substrate binding pocket. Further, we combine computational modeling with functional studies to unravel the molecular determinants involved in NDCBE and SLC4 transport. The mechanisms involved in SLC4-mediated ion transport are still under debate. Here, the authors present a cryoEM structure of the Sodium-driven Chloride/Bicarbonate Exchanger NDCBE, which - together with computational modeling and mutagenesis - reveals molecular determinants of ion transport by SLC4.
- Subjects
BICARBONATE ions; CHLORIDE channels; IONS; CHLORIDES; SODIUM ions; AMILORIDE
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-25998-2