title: Mechanism and significance of P4 ATPase-catalyzed lipid transport: lessons from a Na+/K+-pump.
abstract: Members of the P(4) subfamily of P-type ATPases are believed to catalyze phospholipid transport across membrane bilayers, a process influencing a host of cellular functions. Atomic structures and functional analysis of P-type ATPases that pump small cations and metal ions revealed a transport mechanism that appears to be conserved throughout the family. A challenging problem is to understand how this mechanism is adapted in P(4) ATPases to flip phospholipids. P(4) ATPases form oligomeric complexes with members of the CDC50 protein family. While formation of these complexes is required for P(4) ATPase export from the endoplasmic reticulum, little is known about the functional role of the CDC50 subunits. The Na(+)/K(+)-ATPase and closely-related H(+)/K(+)-ATPase are the only other P-type pumps that are oligomeric, comprising mandatory beta-subunits that are strikingly reminiscent of CDC50 proteins. Besides serving a role in the functional maturation of the catalytic alpha-subunit, the beta-subunit also contributes specifically to intrinsic transport properties of the Na(+)/K(+) pump. As beta-subunits and CDC50 proteins likely adopted similar structures to accomplish analogous tasks, current knowledge of the Na(+)/K(+)-ATPase provides a useful guide for understanding the inner workings of the P(4) ATPase class of lipid pumps.
authors.affiliation: Membrane Enzymology, Bijvoet Center and Institute of Biomembranes, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Catheleyne F
authors.initials: CF
authors.lastname: Puts
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Holthuis
mesh_terms: D000251:Adenosine Triphosphatases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002384:Catalysis; D008051:Lipid Bilayers / Q000378:metabolism; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase