Structural similarities of Na,K-ATPase and SERCA, the Ca2+-ATPase of the sarcoplasmic reticulum

The crystal structure of SERCA1a (skeletal-muscle sarcoplasmic-reticulum /e ndoplasmic-reticulum Ca2+-ATPase) has recently been determined at 2.6 Angst rom (note 1 Angstrom = 0.1nm) resolution [Toyoshima, Nakasako, Nomura and O gawa (2000) Nature (London) 405, 647-655]. Other P-type ATPases are thought to share key features of the ATP hydrolysis site and a central core of tra nsmembrane helices. Outside of these most-conserved segments, structural si milarities are less certain, and predicted transmembrane topology differs b etween subclasses. In the present review the homologous regions of several representative P-type ATPases are aligned with the SERCA sequence and mappe d on to the SERCA structure for comparison. Homology between SERCA and the Na,K-ATPase is more extensive than with any other ATPase, even PMCA, the Ca 2+-ATPase of plasma membrane. Structural features of the Na,K-ATPase are pr ojected on to the Ca2+-ATPase crystal structure to assess the likelihood th at they share the same fold. Homology extends through all ten transmembrane spans, and most insertions and deletions are predicted to be at the surfac e. The locations of specific residues are examined, such as proteolytic cle avage sites, intramolecular cross-linking sites. and the binding sites of c ertain other proteins. On the whole, the similarity supports a shared fold, with some particular exceptions.