Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE

Weiguang Wang, Kirill Tsirulnikov, Hristina R. Zhekova, Gülru Kayık, Hanif Muhammad Khan, Rustam Azimov, Natalia Abuladze, Liyo Kao, Debbie Newman, Sergei Yu. Noskov, Z. Hong Zhou, Alexander Pushkin and Ira Kurtz ()
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Weiguang Wang: University of California
Kirill Tsirulnikov: University of California
Hristina R. Zhekova: University of Calgary
Gülru Kayık: University of Calgary
Hanif Muhammad Khan: University of Calgary
Rustam Azimov: University of California
Natalia Abuladze: University of California
Liyo Kao: University of California
Debbie Newman: University of California
Sergei Yu. Noskov: University of Calgary
Z. Hong Zhou: California NanoSystems Institute, University of California
Alexander Pushkin: University of California
Ira Kurtz: University of California

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25998-2

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DOI: 10.1038/s41467-021-25998-2

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