title: Molecular mechanisms of protein-cholesterol interactions in plasma membranes: Functional distinction between topological (tilted) and consensus (CARC/CRAC) domains.
abstract: The molecular mechanisms that control the multiple possible modes of protein association with membrane cholesterol are remarkably convergent. These mechanisms, which include hydrogen bonding, CH-π stacking and dispersion forces, are used by a wide variety of extracellular proteins (e.g. microbial or amyloid) and membrane receptors. Virus fusion peptides penetrate the membrane of host cells with a tilted orientation that is compatible with a transient interaction with cholesterol; this tilted orientation is also characteristic of the process of insertion of amyloid proteins that subsequently form oligomeric pores in the plasma membrane of brain cells. Membrane receptors that are associated with cholesterol generally display linear consensus binding motifs (CARC and CRAC) characterized by a triad of basic (Lys/Arg), aromatic (Tyr/phe) and aliphatic (Leu/Val) amino acid residues. In some cases, the presence of both CARC and CRAC within the same membrane-spanning domain allows the simultaneous binding of two cholesterol molecules, one in each membrane leaflet. In this review the molecular basis and the functional significance of the different modes of protein-cholesterol interactions in plasma membranes are discussed.
authors.affiliation: EA-4674, Interactions Moléculaires et Systèmes Membranaires, Aix-Marseille Université, Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Fantini
authors.affiliation: EA-4674, Interactions Moléculaires et Systèmes Membranaires, Aix-Marseille Université, Marseille, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Di Scala
authors.affiliation: Laboratory of Molecular Neurobiology, Institute for Biomedical Research (BIOMED), Faculty of Medical Sciences, UCA-CONICET, Av. Alicia Moreau de Justo 1600, C1107AFF Buenos Aires, Argentina.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Baier
authors.affiliation: Laboratory of Molecular Neurobiology, Institute for Biomedical Research (BIOMED), Faculty of Medical Sciences, UCA-CONICET, Av. Alicia Moreau de Justo 1600, C1107AFF Buenos Aires, Argentina. Electronic address: rtfjb1@yahoo.com.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Barrantes
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D016384:Consensus Sequence; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D000072417:Protein Domains
chemical_list: D008565:Membrane Proteins; D002784:Cholesterol
keywords: Cholesterol; Cholesterol consensus motifs; Cholesterol-lipid interactions; Protein-lipid interactions