title: Transmembrane segments of the P-type cation-transporting ATPases. A comparative study.
abstract: The transmembrane segments predicted for the Neurospora H-ATPase are laid out diagrammatically in Figure 10. Although the eight segments have arbitrarily been compressed into rectangles of the same size, they range in length from 20 residues (II) to 30 residues (IV and VI), so the corresponding helices must vary in length as well. Notable features of the model include the charged residues located just outside the plane of the membrane, with a clear excess of negative charges (5-, 1+) at the extracellular surface and a slight excess of positive charges (4+, 3-) at the cytoplasmic surface. There are also a conspicuous number of bulky residues (tryptophan, phenylalanine, and tyrosine) just inside the plane of the membrane. Within the bilayer, most of the helices are noticeably amphipathic, consistent with the expectation that at least some of them stack together to form a channel-like structure with a hydrophobic surface and a hydrophilic core. The charged residues predicted to lie within the membrane are listed in Table 2, which is a summary of data from eight of the P-type ATPases; the S. cerevisiae and S. pombe enzymes have not been included because they are nearly identical in this respect to the Neurospora enzyme. Interestingly, all of the ATPases have more membrane-embedded negative charges (5 to 8) than positive ones (0 to 4), a pattern that may be connected with their role as cation transporters. Certainly, other unrelated transport proteins have a rather different pattern of positive and negative charges: for example, the mammalian glucose transporter (1+, 2-), Na-glucose transporter (3+, 3-), and the E. coli lac permease (11+, 7-). The actual positioning of the negative charges in the P-type ATPases does not make it easy to single out the functionally important ones, however. The glutamyl residue in segment I is present in the fungal, plant, and Leishmania H-ATPases but not in the gastric H,K-ATPase. The same is true for the aspartate in segment II, except that it also appears in the muscle and brain Ca-ATPases. A glutamate is found at one end of segment III in the E. coli and fungal enzymes and at the other end in Arabidopsis; in segment IV, another glutamate appears in a well-conserved region in the Leishmania and mammalian enzymes but not in the bacterial, fungal, or plant ones.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Human Genetics, Yale School of Medicine, New Haven, Connecticut 06510.
authors.forename: R K
authors.initials: RK
authors.lastname: Nakamoto
authors.forename: R
authors.initials: R
authors.lastname: Rao
authors.forename: C W
authors.initials: CW
authors.lastname: Slayman
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis*; D000595:Amino Acid Sequence; D000252:Calcium-Transporting ATPases / Q000032:analysis; D002462:Cell Membrane / Q000201:enzymology*; D017506:H(+)-K(+)-Exchanging ATPase; D008969:Molecular Sequence Data; D006180:Proton-Translocating ATPases / Q000032:analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis
chemical_list: D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D006180:Proton-Translocating ATPases; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase