Analysis of membrane and surface protein sequences with the hydrophobic moment plot.
An algorithm has been developed which identifies alpha-helices involved in the interactions of membrane proteins with lipid bilayers and which distinguishes them from helices in soluble proteins. The membrane-associated helices are then classified with the aid of the hydrophobic moment plot, on which the hydrophobic moment of each helix is plotted as a function of its hydrophobicity. The magnitude of hydrophobic moment measures the amphiphilicity of the helix (and hence its tendency to seek a surface between hydrophobic and hydrophilic phases), and the hydrophobicity measures its affinity for the membrane interior. Segments of membrane proteins in alpha-helices tend to fall in one of three regions of a hydrophobic moment plot: (1) monomeric transmembrane anchors (class I HLA transmembrane sequences) lie in the region of highest hydrophobicity and smallest hydrophobic moment; (2) helices presumed to be paired (such as the transmembrane M segments of surface immunoglobulins) and helices which are bundled together in membranes (such as bacteriorhodopsin) fall in the adjacent region with higher hydrophobic moment and smaller hydrophobicity; and (3) helices from surface-seeking proteins (such as melittin) fall in the region with still higher hydrophobic moment. alpha-Helices from globular proteins mainly fall in a region of lower mean hydrophobicity and hydrophobic moment. Application of these methods to the sequence of diphtheria toxin suggests four transmembrane helices and a surface-seeking helix in fragment B, the moiety known to have transmembrane function.
D000595:Amino Acid Sequence; D004167:Diphtheria Toxin; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D008433:Mathematics; D008563:Membrane Lipids; D008565:Membrane Proteins; D011487:Protein Conformation; D014867:Water
D004167:Diphtheria Toxin; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D008563:Membrane Lipids; D008565:Membrane Proteins; D014867:Water