複合体: Secretory pathway Ca(2+)-transporting ATPase type 1
タンパク質・ペプチド: Calcium-transporting ATPase type 2C member 1
リガンド: MAGNESIUM ION
リガンド: CALCIUM IONカルシウム
リガンド: BERYLLIUM TRIFLUORIDE ION
キーワード
hSPCA1 / MEMBRANE PROTEIN (膜タンパク質) / METAL TRANSPORT
機能・相同性
機能・相同性情報
Golgi calcium ion homeostasis / Golgi calcium ion transport / P-type manganese transporter activity / trans-Golgi network membrane organization / manganese ion transport / intracellular manganese ion homeostasis / P-type Ca2+ transporter / P-type calcium transporter activity / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / positive regulation of Golgi to plasma membrane protein transport ...Golgi calcium ion homeostasis / Golgi calcium ion transport / P-type manganese transporter activity / trans-Golgi network membrane organization / manganese ion transport / intracellular manganese ion homeostasis / P-type Ca2+ transporter / P-type calcium transporter activity / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / positive regulation of Golgi to plasma membrane protein transport / cis-Golgi network membrane / Golgi cisterna membrane / Ion transport by P-type ATPases / epidermis development / calcium ion transmembrane transport / ゴルジ体 / intracellular calcium ion homeostasis / calcium ion transport / manganese ion binding / actin cytoskeleton organization / positive regulation of canonical NF-kappaB signal transduction / ゴルジ体 / calcium ion binding / ゴルジ体 / 小胞体 / ATP hydrolysis activity / ATP binding / 生体膜 / metal ion binding / 細胞膜 類似検索 - 分子機能
ジャーナル: Cell Res / 年: 2023 タイトル: Structure and transport mechanism of the human calcium pump SPCA1. 著者: Mengqi Wu / Cang Wu / Tiefeng Song / Kewu Pan / Yong Wang / Zhongmin Liu / 要旨: Secretory-pathway Ca-ATPases (SPCAs) play critical roles in maintaining Ca homeostasis, but the exact mechanism of SPCAs-mediated Ca transport remains unclear. Here, we determined six cryo-electron ...Secretory-pathway Ca-ATPases (SPCAs) play critical roles in maintaining Ca homeostasis, but the exact mechanism of SPCAs-mediated Ca transport remains unclear. Here, we determined six cryo-electron microscopy (cryo-EM) structures of human SPCA1 (hSPCA1) in a series of intermediate states, revealing a near-complete conformational cycle. With the aid of molecular dynamics simulations, these structures offer a clear structural basis for Ca entry and release in hSPCA1. We found that hSPCA1 undergoes unique conformational changes during ATP binding and phosphorylation compared to other well-studied P-type II ATPases. In addition, we observed a conformational distortion of the Ca-binding site induced by the separation of transmembrane helices 4L and 6, unveiling a distinct Ca release mechanism. Particularly, we determined a structure of the long-sought CaE2P state of P-type IIA ATPases, providing valuable insights into the Ca transport cycle. Together, these findings enhance our understanding of Ca transport by hSPCA1 and broaden our knowledge of P-type ATPases.