title: ERα17p, a peptide reproducing the hinge region of the estrogen receptor α associates to biological membranes: A biophysical approach.
abstract: Recently, we identified a peptide (ERα17p, P(295)LMIKRSKKNSLALSLT(311)) that corresponds to the 295-311 sequence of the estrogen receptor α (ERα, hinge region) and which exerts a panel of pharmacological effects in breast cancer cells. Remarkably, these effects can result from the interaction of ERα17p with the plasma membrane. Herein, we show that ERα17p adopts a β-sheet secondary structure when in contact with anionic phospholipids and that it is engulfed within the lipid bilayer. While ERα17p increases the fluidity of membrane mimics, it weakly internalizes in living cells. In light of the above, one may evoke one important role of the 295-311 region of the ERα: the corresponding peptide could be secreted/delivered to the extracellular medium to interact with neighboring cells, both intracellularly and at the membrane level. Finally, the 295-311 region of ERα being in proximity to the cystein-447, the palmitoylation site of the ERα raises the question of its involvement in the interaction/stabilization of the protein with the membrane.
authors.affiliation: Laboratoire des BioMolécules, CNRS-UMR 7203, 24 rue Lhomond, Ecole Normale Supérieure/UPMC Univ Paris 06, 75253 Paris Cedex 05, France.
authors.forename: Cillian
authors.initials: C
authors.lastname: Byrne
authors.forename: Lucie
authors.initials: L
authors.lastname: Khemtémourian
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pelekanou
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Guy
authors.initials: G
authors.lastname: Leclercq
authors.forename: Sandrine
authors.initials: S
authors.lastname: Sagan
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burlina
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacquot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004706:Endodeoxyribonucleases; D029968:Escherichia coli Proteins; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D005452:Fluoresceins / Q000737:chemistry; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry; D008560:Membrane Fluidity; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D010715:Phosphatidylglycerols / Q000737:chemistry; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D012015:Reference Standards; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000592:standards; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins; D047628:Estrogen Receptor alpha; D005452:Fluoresceins; D008081:Liposomes; D010446:Peptide Fragments; D010715:Phosphatidylglycerols; C576174:estrogen receptor alpha (295-311), human; C002773:dimyristoylphosphatidylglycerol; D004706:Endodeoxyribonucleases; C448636:Cho protein, E coli; D004134:Dimyristoylphosphatidylcholine; C007740:fluorexon