Structures of the FXYD regulatory proteins in lipid micelles and membranes.
The FXYD membrane proteins constitute a family of conserved auxiliary subunits of the Na,K-ATPase, and have been the focus of recent attention due to their ability to finely regulate the activity of the enzyme complex in various physiological settings. In this review we describe the structures of the proteins, as well as their dynamics and their associations with the lipid bilayer membrane, which we have recently determined by NMR spectroscopy. Although the proteins are relatively small, their genes contain as many as six to nine small exons, and the coincidence of structured protein segments with their genetic elements suggests assembly from discrete structural modules through exon shuffling. The three-dimensional structures and backbone dynamics provide the foundation for understanding their intra-membrane association with the Na,K-ATPase alpha subunit, and the structure of FXYD1 suggests a mechanism whereby the phosphorylation of conserved Ser residues, by protein kinases A and C, could induce a conformational change in the cytoplasmic domain of the protein, to modulate its interaction with the alpha subunit.
Franzin
Carla M
CM
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Gong
Xiao-Min
XM
Teriete
Peter
P
Marassi
Francesca M
FM
D000818:Animals; D002462:Cell Membrane; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008823:Micelles; D009363:Neoplasm Proteins; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D015221:Potassium Channels; D021122:Protein Subunits; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
C091777:FXYD3 protein, human; C094337:Fxyd4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; D008823:Micelles; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D015221:Potassium Channels; D021122:Protein Subunits; C069141:phospholemman; C416502:FXYD2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase