Differentiation of lipid-associating helices by use of three-dimensional molecular hydrophobicity potential calculations.
Several types of lipid-associating helices exist: transmembrane helices such as in receptor proteins, pore-forming helices in ion channel proteins, fusion-inducing peptides in viral proteins, and amphipathic helices such as in plasma apolipoproteins. In order to propose a classification of these helices according to their molecular properties, we introduce the concept of molecular hydrophobicity potential for such helical segments. The calculation of this parameter for alpha-helices enables the visualization of the hydrophobic and hydrophilic envelopes around the peptide and their three-dimensional representation by molecular graphics. We have used this parameter to differentiate between pore-forming helices with a hydrophobic envelope larger than the hydrophilic component, membrane-spanning helices surrounded almost entirely by an hydrophobic envelope, fusiogenic peptides with an hydrophobicity gradient both around the helix and along the axis, and finally, amphipathic helices with a predominantly hydrophilic envelope. The structure of the lipid-protein complexes is determined by a number of different interactions: the hydrophobic interaction of the apolar faces of the helices with lipids, the polar interaction of the hydrophilic sides of different helices with each other, and the interaction of hydrophilic residues with the aqueous solvent. The relative magnitude of the hydrophobic and hydrophilic envelopes accounts for the differences in the structure of the lipid-protein complexes. Purely hydrophobic interactions stabilize transmembrane helical segments, while hydrophobic interactions with the lipid phase and with each other are involved in the stabilization of the pore-forming helices. In contrast, both hydrophobic interactions with the lipids and hydrophilic interactions with the aqueous phase contribute to the arrangement of amphipathic helices around the edges of the discoidal lipid-apoprotein complexes.
Brasseur
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Laboratoire Chimie Physique des Macromolecules aux Interfaces CP 206-2, Université Libre de Bruxelles, Belgium.
D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I; D001053:Apolipoproteins / Q000737:chemistry; D001054:Apolipoproteins A / Q000235:genetics; D002116:Calcitonin / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007473:Ion Channels / Q000737:chemistry; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D012474:Salmon; D014764:Viral Proteins / Q000737:chemistry
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001054:Apolipoproteins A; D007473:Ion Channels; D008055:Lipids; D010455:Peptides; D014764:Viral Proteins; D002116:Calcitonin