7DSV

Structure of a human NHE1-CHP1 complex under pH 6.5

7DSV の概要

• エントリーDOI: 10.2210/pdb7dsv/pdb
• EMDBエントリー: 30847
• 分子名称: Sodium/hydrogen exchanger 1, Calcineurin B homologous protein 1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (3 entities in total)
• 機能のキーワード: transporter, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 160687.61

構造登録者

Dong, Y.,Gao, Y.,Li, B.,Zhang, X.C.,Zhao, Y. (登録日: 2021-01-03, 公開日: 2021-06-23, 最終更新日: 2024-03-27)

主引用文献

Dong, Y.,Gao, Y.,Ilie, A.,Kim, D.,Boucher, A.,Li, B.,Zhang, X.C.,Orlowski, J.,Zhao, Y.
Structure and mechanism of the human NHE1-CHP1 complex.
Nat Commun, 12:3474-3474, 2021

PubMed Abstract: Sodium/proton exchanger 1 (NHE1) is an electroneutral secondary active transporter present on the plasma membrane of most mammalian cells and plays critical roles in regulating intracellular pH and volume homeostasis. Calcineurin B-homologous protein 1 (CHP1) is an obligate binding partner that promotes NHE1 biosynthetic maturation, cell surface expression and pH-sensitivity. Dysfunctions of either protein are associated with neurological disorders. Here, we elucidate structures of the human NHE1-CHP1 complex in both inward- and inhibitor (cariporide)-bound outward-facing conformations. We find that NHE1 assembles as a symmetrical homodimer, with each subunit undergoing an elevator-like conformational change during cation exchange. The cryo-EM map reveals the binding site for the NHE1 inhibitor cariporide, illustrating how inhibitors block transport activity. The CHP1 molecule differentially associates with these two conformational states of each NHE1 monomer, and this association difference probably underlies the regulation of NHE1 pH-sensitivity by CHP1.

PubMed: 34108458
DOI: 10.1038/s41467-021-23496-z

実験手法

ELECTRON MICROSCOPY (3.4 Å)