5MPM

SERCA2a from pig heart

5MPM の概要

• エントリーDOI: 10.2210/pdb5mpm/pdb
• 分子名称: Sarcoplasmic/endoplasmic reticulum calcium ATPase 2, TRIFLUOROMAGNESATE, (6AR,11AS,11BR)-10-ACETYL-9-HYDROXY-7,7-DIMETHYL-2,6,6A,7,11A,11B-HEXAHYDRO-11H-PYRROLO[1',2':2,3]ISOINDOLO[4,5,6-CD]INDOL-11-ONE, ... (6 entities in total)
• 機能のキーワード: ca2+-atpase, serca, hydrolase
• 由来する生物種: Sus scrofa (Pig)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 110342.38

構造登録者

Drachmann, N.D.,Sitsel, A.,Andersen, J.L.,Nissen, P.,Olesen, C. (登録日: 2016-12-16, 公開日: 2018-01-17, 最終更新日: 2024-11-13)

主引用文献

Sitsel, A.,De Raeymaecker, J.,Drachmann, N.D.,Derua, R.,Smaardijk, S.,Andersen, J.L.,Vandecaetsbeek, I.,Chen, J.,De Maeyer, M.,Waelkens, E.,Olesen, C.,Vangheluwe, P.,Nissen, P.
Structures of the heart specific SERCA2a Ca2+-ATPase.
Embo J., 38:-, 2019

PubMed Abstract: The sarcoplasmic/endoplasmic reticulum Ca-ATPase 2a (SERCA2a) performs active reuptake of cytoplasmic Ca and is a major regulator of cardiac muscle contractility. Dysfunction or dysregulation of SERCA2a is associated with heart failure, while restoring its function is considered as a therapeutic strategy to restore cardiac performance. However, its structure has not yet been determined. Based on native, active protein purified from pig ventricular muscle, we present the first crystal structures of SERCA2a, determined in the CPA-stabilized E2-AlF4- form (3.3 Å) and the Ca-occluded [Ca]E1-AMPPCP form (4.0 Å). The structures are similar to the skeletal muscle isoform SERCA1a pointing to a conserved mechanism. We seek to explain the kinetic differences between SERCA1a and SERCA2a. We find that several isoform-specific residues are acceptor sites for post-translational modifications. In addition, molecular dynamics simulations predict that isoform-specific residues support distinct intramolecular interactions in SERCA2a and SERCA1a. Our experimental observations further indicate that isoform-specific intramolecular interactions are functionally relevant, and may explain the kinetic differences between SERCA2a and SERCA1a.

PubMed: 30777856
DOI: 10.15252/embj.2018100020

実験手法

X-RAY DIFFRACTION (3.3 Å)