Figure 2.

Mechanism of Ca²⁺ transport. (A) Schematic overview of the catalytic transport cycle of the sarco(endo)plasmic reticulum Ca²⁺-ATPase 1a (SERCA1a), which is also used as the reference mechanism for other Ca²⁺-ATPases. The cycle is accompanies the description in the main text. Note that after ADP release, a new ATP can immediately bind to the N-domain. (B) Structure of SERCA1a (PDB 3N8G; Bublitz et al. 2013) depicting the major domains in various colors: A, actuator domain (yellow); P, phosphorylation domain (blue); N, nucleotide-binding domain (red), and transmembrane (TM) domain (M1–M10: M1–M2, wheat; M3–M4, brown; M5–M6, dark gray; M7–M10, light gray). Ca²⁺ ions are depicted in dark blue spheres and ATP in green spheres. (C) Detailed image showing the side chains of the coordinating residues in the two Ca²⁺-binding sites in the SERCA1a TM domain (PDB 3N8G). Note that, in total, 10 residues situated on M4, M5, M6, and M8 contribute either via their side chains (depicted) or their backbone oxygen atoms (not shown). Moreover, two H₂O molecules are also involved in Ca²⁺ coordination in site I (not shown). E309 in red is the gating residue. Only the common site II is highly conserved between Golgi/secretory pathway Ca²⁺-ATPase (SPCA), plasma membrane Ca²⁺-ATPase (PMCA), and SERCA.