CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1

Kevin W. Huynh, Jiansen Jiang, Natalia Abuladze, Kirill Tsirulnikov, Liyo Kao, Xuesi Shao, Debra Newman, Rustam Azimov, Alexander Pushkin (), Z. Hong Zhou () and Ira Kurtz ()
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Kevin W. Huynh: University of California
Jiansen Jiang: University of California
Natalia Abuladze: University of California
Kirill Tsirulnikov: University of California
Liyo Kao: University of California
Xuesi Shao: University of California
Debra Newman: University of California
Rustam Azimov: University of California
Alexander Pushkin: University of California
Z. Hong Zhou: University of California
Ira Kurtz: University of California

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract Na+-coupled acid–base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na+-coupled acid–base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03271-3

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DOI: 10.1038/s41467-018-03271-3

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