6CAA

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

Summary for 6CAA

• Entry DOI: 10.2210/pdb6caa/pdb
• EMDB information: 7441
• Descriptor: Electrogenic sodium bicarbonate cotransporter 1 (1 entity in total)
• Functional Keywords: slc4a4, electrogenic sodium-coupled bicarbonate cotransporters, transport protein, nbce1
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 232344.62

Authors

Huynh, K.W.,Jiang, J.,Abuladze, N.,Tsirulnikov, K.,Kao, L.,Shao, X.,Newman, D.,Azimov, R.,Pushkin, A.,Zhou, Z.H.,Kurtz, I. (deposition date: 2018-01-29, release date: 2018-03-07, Last modification date: 2024-03-13)

Primary citation

Huynh, K.W.,Jiang, J.,Abuladze, N.,Tsirulnikov, K.,Kao, L.,Shao, X.,Newman, D.,Azimov, R.,Pushkin, A.,Zhou, Z.H.,Kurtz, I.
CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.
Nat Commun, 9:900-900, 2018

PubMed 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.

PubMed: 29500354
DOI: 10.1038/s41467-018-03271-3

Experimental method

ELECTRON MICROSCOPY (3.9 Å)