Structures of the heart specific SERCA2a Ca²⁺-ATPase.

ABSTRACT: The sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 2a (SERCA2a) performs active reuptake of cytoplasmic Ca²⁺ 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 Ca²⁺-occluded [Ca₂]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 di

SUBMITTER: Sitsel A 

PROVIDER: S-EPMC6396164 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature