Hydropathy Plots and the Prediction of Membrane Protein Topology

Plots of sliding-window averages of amino acid properties taken along amino acid sequences provide useful structural insights for both soluble (Rose, 1978; Rose and Roy, 1980; Kyte and Doolittle, 1982) and membrane (Argos et al., 1982; Kyte and Doolittle, 1982; Engelman et al., 1986) proteins. They have been especially important for membrane proteins, however, because the determination of three-dimensional structures is more problematic. The database of high-resolution crystallographic membrane protein structures contains only five examples of two types of proteins: two photosynthetic reaction centers (PSRC) from Rhodopseudomonas viridis (Deisenhofer et al., 1985) and Rhodobacter sphaeroides (Allen et al., 1987), a porin from Rhodobacter capsulatus (Weiss et al., 1991a), and two porins from Escherichia coli (Cowan et al., 1992). An excellent, but incomplete, structural model for bacteriorhodopsin (BR) from Halobacterium halobium has been determined by Henderson et al. (1990) using electron diffraction methods. More recently, an atomic model of plant light-harvesting complex, also determined by electron diffraction, has been reported by Kuhlbrandt et al. (1994).