ERα17p, a peptide reproducing the hinge region of the estrogen receptor α associates to biological membranes: A biophysical approach

Recently, we identified a peptide (ERα17p, P295LMIKRSKKNSLALSLT311) 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.

► We explore the interaction of the 295–311 sequence of ERα with membrane mimics.
► CD, DSC and calcein leakage assays suggest electrostatic contacts with negative lipids.
► This peptide is internalized, even modestly, in CHO cells.
► This confirms a peptide/membrane contact in living cells.
► The 295–311 motif of ERα could participate in its anchoring with the plasma membrane.