title: The C-terminal transmembrane domain of human phospholipid scramblase 1 is essential for the protein flip-flop activity and Ca²⁺-binding.
abstract: Human phospholipid scramblase 1 (SCR) is a 318 amino acid protein that was originally described as catalyzing phospholipid transbilayer (flip-flop) motion in plasma membranes in a Ca²⁺-dependent, ATP-independent way. Further studies have suggested an intranuclear role for this protein in addition. A putative transmembrane domain located at the C terminus (aa 291-309) has been related to the flip-flop catalysis. In order to clarify the role of the C-terminal region of SCR, a mutant was produced (SCRΔ) in which the last 28 amino acid residues were lacking, including the α-helix. SCRΔ had lost the scramblase activity and its affinity for Ca²⁺ was decreased by one order of magnitude. Fluorescence and IR spectroscopic studies revealed that the C-terminal region of SCR was essential for the proper folding of the protein. Moreover, it was found that Ca²⁺ exerted an overall destabilizing effect on SCR, which might facilitate its binding to membranes.
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080, Bilbao, Spain.
authors.forename: Lissete
authors.initials: L
authors.lastname: Sánchez-Magraner
authors.forename: Itziar M D
authors.initials: IM
authors.lastname: Posada
authors.forename: Nagore
authors.initials: N
authors.lastname: Andraka
authors.forename: F Xabier
authors.initials: FX
authors.lastname: Contreras
authors.forename: Ana R
authors.initials: AR
authors.lastname: Viguera
authors.forename: Diego M A
authors.initials: DM
authors.lastname: Guérin
authors.forename: José L R
authors.initials: JL
authors.lastname: Arrondo
authors.forename: Hugo L
authors.initials: HL
authors.lastname: Monaco
authors.forename: Félix M
authors.initials: FM
authors.lastname: Goñi
mesh_terms: D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D050356:Lipid Metabolism; D009154:Mutation; D049294:Phospholipid Transfer Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
chemical_list: C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; D011993:Recombinant Fusion Proteins; D002118:Calcium