9PS2

Cryo-EM structure of NCLX with calcium (class 4a)

9PS2 の概要

• エントリーDOI: 10.2210/pdb9ps2/pdb
• EMDBエントリー: 71820
• 分子名称: NCLX, CALCIUM ION (3 entities in total)
• 機能のキーワード: membrane transporter, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 192233.30

構造登録者

Zhang, J.,Feng, L. (登録日: 2025-07-24, 公開日: 2025-09-10, 最終更新日: 2025-11-05)

主引用文献

Fan, M.,Tsai, C.W.,Zhang, J.,Zhang, J.,Krishnan, A.R.,Liu, T.Y.,Huang, Y.L.,Aydin, D.,Du, S.,Sobecks, B.L.,Rodriguez, M.X.,Reiter, A.H.,Bertozzi, C.R.,Dror, R.O.,Tsai, M.F.,Feng, L.
Structure and mechanism of the mitochondrial calcium transporter NCLX.
Nature, 646:1272-1280, 2025

PubMed Abstract: As a key mitochondrial Ca transporter, NCLX regulates intracellular Ca signalling and vital mitochondrial processes. The importance of NCLX in cardiac and nervous-system physiology is reflected by acute heart failure and neurodegenerative disorders caused by its malfunction. Despite substantial advances in the field, the transport mechanisms of NCLX remain unclear. Here we report the cryo-electron microscopy structures of NCLX, revealing its architecture, assembly, major conformational states and a previously undescribed mechanism for alternating access. Functional analyses further reveal an unexpected transport function of NCLX as a H/Ca exchanger, rather than as a Na/Ca exchanger as widely believed. These findings provide critical insights into mitochondrial Ca homeostasis and signalling, offering clues for developing therapies to treat diseases related to abnormal mitochondrial Ca.

PubMed: 40931067
DOI: 10.1038/s41586-025-09491-0

実験手法

ELECTRON MICROSCOPY (2.15 Å)