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8SGI

Cryo-EM structure of human NCX1 in complex with SEA0400

8SGI の概要
エントリーDOI10.2210/pdb8sgi/pdb
EMDBエントリー40456
分子名称Sodium/calcium exchanger 1, Fab light chain, Fab heavy chain, ... (7 entities in total)
機能のキーワードna/ca exchanger, sodium calcium exchanger, transport protein
由来する生物種Homo sapiens (human)
詳細
タンパク質・核酸の鎖数3
化学式量合計158037.57
構造登録者
Xue, J.,Jiang, Y. (登録日: 2023-04-12, 公開日: 2024-04-24, 最終更新日: 2025-06-04)
主引用文献Xue, J.,Zeng, W.,John, S.,Attiq, N.,Ottolia, M.,Jiang, Y.
Structural mechanisms of PIP 2 activation and SEA0400 inhibition in human cardiac sodium-calcium exchanger NCX1.
Elife, 14:-, 2025
Cited by
PubMed Abstract: Na/Ca exchangers (NCXs) transport Ca across the plasma membrane in exchange for Na and play a vital role in maintaining cellular Ca homeostasis. Our previous structural study of human cardiac NCX1 (HsNCX1) reveals the overall architecture of the eukaryotic exchanger and the formation of the inactivation assembly by the intracellular regulatory domain that underlies the cytosolic Na-dependent inactivation and Ca activation of NCX1. Here, we present the cryo-EM structures of HsNCX1 in complex with a physiological activator phosphatidylinositol 4,5-bisphosphate (PIP), or pharmacological inhibitor SEA0400, that enhances the inactivation of the exchanger. We demonstrate that PIP binding stimulates NCX1 activity by inducing a conformational change at the interface between the transmembrane (TM) and cytosolic domains that destabilizes the inactivation assembly. In contrast, SEA0400 binding in the TM domain of NCX1 stabilizes the exchanger in an inward-facing conformation that facilitates the formation of the inactivation assembly, thereby promoting the Na-dependent inactivation of NCX1. Thus, this study reveals the structural basis of PIP activation and SEA0400 inhibition of NCX1 and provides some mechanistic understandings of cellular regulation and pharmacology of NCX family proteins.
PubMed: 40433952
DOI: 10.7554/eLife.105396
主引用文献が同じPDBエントリー
実験手法
ELECTRON MICROSCOPY (2.9 Å)
構造検証レポート
Validation report summary of 8sgi
検証レポート(詳細版)ダウンロードをダウンロード

237992

件を2025-06-25に公開中

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