7YAG

CryoEM structure of SPCA1a in E1-Ca-AMPPCP state subclass 1

7YAG の概要

• エントリーDOI: 10.2210/pdb7yag/pdb
• EMDBエントリー: 33711
• 分子名称: Calcium-transporting ATPase type 2C member 1, nanobody head piece of megabody, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (4 entities in total)
• 機能のキーワード: golgi ca2+/mn2+ transporter, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 118019.75

構造登録者

Chen, Z.,Watanabe, S.,Inaba, K. (登録日: 2022-06-28, 公開日: 2023-03-22, 最終更新日: 2025-07-02)

主引用文献

Chen, Z.,Watanabe, S.,Hashida, H.,Inoue, M.,Daigaku, Y.,Kikkawa, M.,Inaba, K.
Cryo-EM structures of human SPCA1a reveal the mechanism of Ca 2+ /Mn 2+ transport into the Golgi apparatus.
Sci Adv, 9:eadd9742-eadd9742, 2023

PubMed Abstract: Secretory pathway Ca/Mn ATPase 1 (SPCA1) actively transports cytosolic Ca and Mn into the Golgi lumen, playing a crucial role in cellular calcium and manganese homeostasis. Detrimental mutations of the gene encoding SPCA1 cause Hailey-Hailey disease. Here, using nanobody/megabody technologies, we determined cryo-electron microscopy structures of human SPCA1a in the ATP and Ca/Mn-bound (E1-ATP) state and the metal-free phosphorylated (E2P) state at 3.1- to 3.3-Å resolutions. The structures revealed that Ca and Mn share the same metal ion-binding pocket with similar but notably different coordination geometries in the transmembrane domain, corresponding to the second Ca-binding site in sarco/endoplasmic reticulum Ca-ATPase (SERCA). In the E1-ATP to E2P transition, SPCA1a undergoes similar domain rearrangements to those of SERCA. Meanwhile, SPCA1a shows larger conformational and positional flexibility of the second and sixth transmembrane helices, possibly explaining its wider metal ion specificity. These structural findings illuminate the unique mechanisms of SPCA1a-mediated Ca/Mn transport.

PubMed: 36867705
DOI: 10.1126/sciadv.add9742

実験手法

ELECTRON MICROSCOPY (3.1 Å)