Abstract
AbstractSLC4 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference62 articles.
1. Liu, Y., Yang, J. & Chen, L. M. Structure and function of SLC4 family transporters. Front. Physiol. 6, 355 (2015).
2. Pushkin, A. & Kurtz, I. SLC4 base (HCO3‾, CO32‾) transporters: classification, function, structure, genetic diseases and knockout models. Am. J. Physiol. 290, 580–599 (2006).
3. Kao, L. et al. SLC4A11 function: evidence for H+(OH‾) and NH3-H+ transport. Am. J. Physiol. Cell Physiol. 318, C392–C405 (2020).
4. Grichtchenko, I. I. et al. Cloning, characterization, and chromosomal mapping of human electroneutral Na+-driven Cl-HCO3 exchanger. J. Biol. Chem. 276, 8358–8363 (2001).
5. Aalkjaer, C., Boedtkjer, E., Choi, I. & Lee, S. Cation-coupled bicarbonate transporters. Compr. Physiol. 4, 1605–1637 (2014).
Cited by
33 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献