Structural Dissection of Epsin-1 N-Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature.

Chemistry (Weinheim an der Bergstrasse, Germany) 2023 May 22

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Spatiotemporal structural alterations in cellular membranes are the hallmark of many vital processes. In these cellular events, the induction of local changes in membrane curvature often plays a pivotal role. Many amphiphilic peptides are able to modulate membrane curvature, but there is little information on specific structural factors that direct the curvature change. Epsin-1 is a representative protein thought to initiate invagination of the plasma membrane upon clathrin-coated vesicles formation. Its N-terminal helical segment (EpN18) plays a key role in inducing positive membrane curvature. This study aimed to elucidate the essential structural features of EpN18 in order to better understand general curvature-inducing mechanisms, and to design effective tools for rationally controlling membrane curvature. Structural dissection of peptides derived from EpN18 revealed the decisive contribution of hydrophobic residues to (i) enhancing membrane interactions, (ii) helix structuring, (iii) inducing positive membrane curvature, and (iv) loosening lipid packing. The strongest effect was obtained by substitution with leucine residues, as this EpN18 analog showed a marked ability to promote the influx of octa-arginine cell-penetrating peptides into living cells. © 2023 Wiley-VCH GmbH.

Citation

Motoki Nishimura, Yoshimasa Kawaguchi, Kakeru Kuroki, Yuna Nakagawa, Toshihiro Masuda, Takayuki Sakai, Kenichi Kawano, Hisaaki Hirose, Miki Imanishi, Tomoka Takatani-Nakase, Sergii Afonin, Anne S Ulrich, Shiroh Futaki. Structural Dissection of Epsin-1 N-Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature. Chemistry (Weinheim an der Bergstrasse, Germany). 2023 May 22;29(29):e202300129