title: A cholesterol recognition motif in human phospholipid scramblase 1.
abstract: Human phospholipid scramblase 1 (SCR) catalyzes phospholipid transmembrane (flip-flop) motion. This protein is assumed to bind the membrane hydrophobic core through a transmembrane domain (TMD) as well as via covalently bound palmitoyl residues. Here, we explore the possible interaction of the SCR TMD with cholesterol by using a variety of experimental and computational biophysical approaches. Our findings indicate that SCR contains an amino acid segment at the C-terminal region that shows a remarkable affinity for cholesterol, although it lacks the CRAC sequence. Other 3-OH sterols, but not steroids lacking the 3-OH group, also bind this region of the protein. The newly identified cholesterol-binding region is located partly at the C-terminal portion of the TMD and partly in the first amino acid residues in the SCR C-terminal extracellular coil. This finding could be related to the previously described affinity of SCR for cholesterol-rich domains in membranes.
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), Departamento de Bioquímica y Biología Molecular, Bilbao, Spain.
authors.forename: Itziar M D
authors.initials: IM
authors.lastname: Posada
authors.affiliation: Interactions Moléculaires et Systèmes Membranaires, EA-4674, Aix-Marseille Université, Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Fantini
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), Departamento de Bioquímica y Biología Molecular, Bilbao, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
authors.forename: F Xabier
authors.initials: FX
authors.lastname: Contreras
authors.affiliation: Laboratory of Molecular Neurobiology, Faculty of Medical Sciences, Biomedical Research Institute (BIOMED) UCA-CONICET, Catholic University of Argentina, Buenos Aires, Argentina.
authors.forename: Francisco
authors.initials: F
authors.lastname: Barrantes
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), Departamento de Bioquímica y Biología Molecular, Bilbao, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), Departamento de Bioquímica y Biología Molecular, Bilbao, Spain. Electronic address: felix.goni@ehu.es.
authors.forename: Félix M
authors.initials: FM
authors.lastname: Goñi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D008051:Lipid Bilayers; C493422:PLSCR1 protein, human; D010446:Peptide Fragments; D049294:Phospholipid Transfer Proteins; D002784:Cholesterol