title: Human endomembrane H+ pump strongly resembles the ATP-synthetase of Archaebacteria.
abstract: Preparations of mammalian H+ pumps that acidify intracellular vesicles contain eight or nine polypeptides, ranging in size from 116 to 17 kDa. Biochemical analysis indicates that the 70- and 58-kDa polypeptides are subunits critical for ATP hydrolysis. The amino acid sequences of the major catalytic subunits (58 and 70 kDa) of the endomembrane H+ pump are unknown from animal cells. We report here the complete sequence of the 58-kDa subunit derived from a human kidney cDNA clone and partial sequences of the 70- and 58-kDa subunits purified from clathrin-coated vesicles of bovine brain. The amino acid sequences of both proteins strongly resemble the sequences of the corresponding subunits of the vacuolar H+ pumps of Archaebacteria, plants, and fungi. The archaebacterial enzyme is believed to use a H+ gradient to synthesize ATP. Thus, a common ancestral protein has given rise to a H+ pump that synthesizes ATP in one organism and hydrolyzes it in another and is highly conserved from prokaryotes to humans. The same pump appears to mediate the acidification of intracellular organelles, including coated vesicles, lysosomes, and secretory granules, as well as extracellular fluids such as urine.
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235-9040.
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: V A
authors.initials: VA
authors.lastname: Fried
authors.forename: D K
authors.initials: DK
authors.lastname: Stone
authors.forename: P A
authors.initials: PA
authors.lastname: Johnston
authors.forename: X S
authors.initials: XS
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D001105:Archaea / Q000201:enzymology / Q000235:genetics*; D001419:Bacteria / Q000235:genetics*; D001483:Base Sequence; D005075:Biological Evolution; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D006180:Proton-Translocating ATPases / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D046911:Macromolecular Substances; D006180:Proton-Translocating ATPases