An alternative model for the transmembrane segments of the yeast H+-ATPase

An alternative topological model for the yeast plasma membrane Ht-ATPase fr om K. lactis was deduced by joint prediction, using 11 algorithms for the p rediction of transmembrane segments complemented with hydrophobic moment an alysis. Similarly to the model currently used in the literature, this alter native model contains 10 transmembrane segments, four in the N-half and six in the C-half of the protein. However, the distribution of the membrane-as sociated segments on the C-half of the enzyme differs in both models. Nine of the 10 transmembrane segments are highly hydrophobic with low hydrophobi c moments, and are probably involved in structural roles. The fifth transme mbrane segment is, on the other hand, less hydrophobic, with the highest hy drophobic moment, suggesting that this segment might have a dynamic role in the coupling of the hydrolysis of ATP with the translocation of protons ac ross the membrane. The alignment of the Ca2+-ATPase, the Na+/K+-ATPase and the Ht-ATPase sequences showed that these proteins have the same topology i n the N-half, but important differences were found at the C-half of the enz ymes. In contrast with the mammalian ATPases, the fifth transmembrane segme nt in the H+-ATPase appears early in the sequence, giving rise to a shorter cytoplasmic central loop. This alternative model will be useful in the des igning of site-directed mutagenesis experiments and contains information fo r the fitting of the amino acid sequence into the transmembrane region of t he three-dimensional model of the ATPase. Copyright (C) 1999 John Wiley & S ons, Ltd.