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547 A calcium pump made visible Anthony G Lee The first high-resolution structure of a P-type ATPase, that of which the two Ca2+-binding sites are low affinity and the Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum, inward facing. Following loss of Ca2+ from these sites to was published in 2000. This structure has provided many clues the lumen of the SR, the ATPase dephosphorylates and to how the Ca2+-ATPase might work, but no complete recycles to E1. answers. The Ca2+-ATPase structure reveals no clear pathway from the cytoplasmic side of the membrane to the pair of high- The simplest structural interpretation of the reaction affinity binding sites for Ca2+ located in the transmembrane scheme is the alternating site model (Figure 1), in which a region of the ATPase and no clear pathway from these sites to single pair of Ca2+ ion binding sites transforms from a the lumenal side of the membrane. The ATPase is therefore state of high affinity exposed to the cytoplasm in E1 to a very unlike an ion channel in its construction. It is unclear from state of low affinity exposed to the lumen in the E2PCa2 the crystal structure of the Ca2+-ATPase exactly how the phosphorylated form. Unfortunately, this simple picture is protein sits within the lipid bilayer that surrounds it in the incomplete, because studies of the effects of lumenal membrane. The Ca2+-ATPase is implicated in thermogenesis in Ca2+ on the level of phosphorylation of the ATPase by some types of muscle; this could involve processes of slippage Pi show that, as well as the pair of cytoplasmic sites, the and leak modulated by interaction between the Ca2+-ATPase Ca2+-ATPase must possess a separate pair of lumenal sites and sarcolipin. [4]. This led to a four-site model for transport, in which Ca2+