Cryo-EM Structure of the Sodium-driven Chloride/bicarbonate Exchanger NDCBE

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Sep 29

PMID 34584093

Citations 23

Authors

Weiguang Wang

Kirill Tsirulnikov

Hristina R Zhekova

Gulru Kayik

Hanif Muhammad Khan

Rustam Azimov

Natalia Abuladze

Liyo Kao

Debbie Newman

Sergei Yu Noskov

Z Hong Zhou

Alexander Pushkin

Ira Kurtz

Affiliations

Soon will be listed here.

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.

Citing Articles

On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations.

Pushkin A, Kao L, Zhekova H, Azimov R, Abuladze N, Shao X Front Physiol. 2025; 15:1474628.

PMID: 39872416 PMC: 11769940. DOI: 10.3389/fphys.2024.1474628.

Molecular insights into the elevator-type mechanism of the cyanobacterial bicarbonate transporter BicA.

Chan M, Alfawaz Y, Paul A, Shukla D Biophys J. 2024; 124(2):379-392.

PMID: 39674889 PMC: 11788499. DOI: 10.1016/j.bpj.2024.12.013.

The Bor1 elevator transport cycle is subject to autoinhibition and activation.

Jiang Y, Jiang J Nat Commun. 2024; 15(1):9090.

PMID: 39433547 PMC: 11494103. DOI: 10.1038/s41467-024-53411-1.

Interdomain-linkers control conformational transitions in the SLC23 elevator transporter UraA.

Kuhn B, Zoller J, Zimmermann I, Gemeinhardt T, Ozkul D, Langer J Nat Commun. 2024; 15(1):7518.

PMID: 39209842 PMC: 11362169. DOI: 10.1038/s41467-024-51814-8.

The structural insight into the functional modulation of human anion exchanger 3.

Jian L, Zhang Q, Yao D, Wang Q, Chen M, Xia Y Nat Commun. 2024; 15(1):6134.

PMID: 39033175 PMC: 11271275. DOI: 10.1038/s41467-024-50572-x.

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