Crystal structure of the plasma membrane proton pump.
A prerequisite for life is the ability to maintain electrochemical imbalances across biomembranes. In all eukaryotes the plasma membrane potential and secondary transport systems are energized by the activity of P-type ATPase membrane proteins: H+-ATPase (the proton pump) in plants and fungi, and Na+,K+-ATPase (the sodium-potassium pump) in animals. The name P-type derives from the fact that these proteins exploit a phosphorylated reaction cycle intermediate of ATP hydrolysis. The plasma membrane proton pumps belong to the type III P-type ATPase subfamily, whereas Na+,K+-ATPase and Ca2+-ATPase are type II. Electron microscopy has revealed the overall shape of proton pumps, however, an atomic structure has been lacking. Here we present the first structure of a P-type proton pump determined by X-ray crystallography. Ten transmembrane helices and three cytoplasmic domains define the functional unit of ATP-coupled proton transport across the plasma membrane, and the structure is locked in a functional state not previously observed in P-type ATPases. The transmembrane domain reveals a large cavity, which is likely to be filled with water, located near the middle of the membrane plane where it is lined by conserved hydrophilic and charged residues. Proton transport against a high membrane potential is readily explained by this structural arrangement.
Pedersen
Bjørn P
BP
Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Denmark.
Buch-Pedersen
Morten J
MJ
Morth
J Preben
JP
Palmgren
Michael G
MG
Nissen
Poul
P
D017360:Arabidopsis / Q000201:enzymology*; D001665:Binding Sites; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology*; D018360:Crystallography, X-Ray; D017136:Ion Transport; D008958:Models, Molecular; D010766:Phosphorylation; D017494:Proton Pumps / Q000737:chemistry* / Q000378:metabolism; D011522:Protons; D055672:Static Electricity; D040681:Structural Homology, Protein
D017494:Proton Pumps; D011522:Protons; D000252:Calcium-Transporting ATPases