The structural basis for coupling of Ca2+ transport to ATP hydrolysis by the sarcoplasmic reticulum Ca2+-ATPase.

Recently, a series of structure determinations has nearly completed a structural description of the transport cycle of the sarcoplasmic reticulum Ca(2+)-ATPase, especially those steps concerned with the phosphorylation by ATP and the dephosphorylation reaction. From these structures Ca(2+)-ATPase emerges as a molecular machine, where globular cytosolic domains and transmembrane helices work in concert like a mechanical pump, as can be vividly demonstrated in animated versions of the pump cycle. The structures show that both ATP phosphorylation and dephosphorylation at Asp351 take place as nucleophilic SN2 reactions, which are associated with Ca(2+) and H(+) occluded states, respectively. These transitory steps ensure efficient coupling between Ca(2+) transport and ATP hydrolysis.