6JJU

Structure of Ca2+ ATPase

6JJU の概要

• エントリーDOI: 10.2210/pdb6jju/pdb
• 分子名称: Sarcoplasmic/endoplasmic reticulum calcium ATPase 2, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: p-type atpase, calcium transport, endoplasmic reticulum, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 113306.73

構造登録者

Inoue, M.,Sakuta, N.,Watanabe, S.,Inaba, K. (登録日: 2019-02-27, 公開日: 2019-05-22, 最終更新日: 2023-11-22)

主引用文献

Inoue, M.,Sakuta, N.,Watanabe, S.,Zhang, Y.,Yoshikaie, K.,Tanaka, Y.,Ushioda, R.,Kato, Y.,Takagi, J.,Tsukazaki, T.,Nagata, K.,Inaba, K.
Structural Basis of Sarco/Endoplasmic Reticulum Ca2+-ATPase 2b Regulation via Transmembrane Helix Interplay.
Cell Rep, 27:1221-1230.e3, 2019

PubMed Abstract: Sarco/endoplasmic reticulum (ER) Ca-ATPase 2b (SERCA2b) is a ubiquitously expressed membrane protein that facilitates Ca uptake from the cytosol to the ER. SERCA2b includes a characteristic 11 transmembrane helix (TM11) followed by a luminal tail, but the structural basis of SERCA regulation by these C-terminal segments remains unclear. Here, we determined the crystal structures of SERCA2b and its C-terminal splicing variant SERCA2a, both in the E1-2Ca-adenylyl methylenediphosphonate (AMPPCP) state. Despite discrepancies with the previously reported structural model of SERCA2b, TM11 was found to be located adjacent to TM10 and to interact weakly with a part of the L8/9 loop and the N-terminal end of TM10, thereby inhibiting the SERCA2b catalytic cycle. Accordingly, mutational disruption of the interactions between TM11 and its neighboring residues caused SERCA2b to display SERCA2a-like ATPase activity. We propose that TM11 serves as a key modulator of SERCA2b activity by fine-tuning the intramolecular interactions with other transmembrane regions.

PubMed: 31018135
DOI: 10.1016/j.celrep.2019.03.106

実験手法

X-RAY DIFFRACTION (3.2 Å)