Tracking Ca ATPase intermediates in real time by x-ray solution scattering.

Sarco/endoplasmic reticulum Ca ATPase (SERCA) transporters regulate calcium signaling by active calcium ion reuptake to internal stores. Structural transitions associated with transport have been characterized by x-ray crystallography, but critical intermediates involved in the accessibility switch across the membrane are missing. We combined time-resolved x-ray solution scattering (TR-XSS) experiments and molecular dynamics (MD) simulations for real-time tracking of concerted SERCA reaction cycle dynamics in the native membrane.

Primary Active Ca Transport Systems in Health and Disease.

Calcium ions (Ca) are prominent cell signaling effectors that regulate a wide variety of cellular processes. Among the different players in Ca homeostasis, primary active Ca transporters are responsible for keeping low basal Ca levels in the cytosol while establishing steep Ca gradients across intracellular membranes or the plasma membrane. This review summarizes our current knowledge on the three types of primary active Ca-ATPases: the sarco(endo)plasmic reticulum Ca-ATPase (SERCA) pumps, the secretory pathway Ca- ATPase (SPCA) isoforms, and the plasma membrane Ca-ATPase (PMCA) Ca-transporters.

Structures of the heart specific SERCA2a Ca-ATPase.

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.