6CAA

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

6CAA の概要

• エントリーDOI: 10.2210/pdb6caa/pdb
• EMDBエントリー: 7441
• 分子名称: Electrogenic sodium bicarbonate cotransporter 1 (1 entity in total)
• 機能のキーワード: slc4a4, electrogenic sodium-coupled bicarbonate cotransporters, transport protein, nbce1
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 232344.62

構造登録者

Huynh, K.W.,Jiang, J.,Abuladze, N.,Tsirulnikov, K.,Kao, L.,Shao, X.,Newman, D.,Azimov, R.,Pushkin, A.,Zhou, Z.H.,Kurtz, I. (登録日: 2018-01-29, 公開日: 2018-03-07, 最終更新日: 2024-03-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.9 Å)