Structural Dissection of Epsin‐1 N‐Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature
Structural Dissection of Epsin‐1 N‐Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature
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Epsin-1 N 末端螺旋肽的结构剖析：疏水残基在调节膜曲率中的作用
DOI：
10.1002/chem.202300129
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Shiroh Futaki
中科院分区：
文献类型：
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作者：
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
细胞膜的时空结构改变是许多生命过程的标志。在这些细胞事件中，膜曲率局部变化的诱导通常起着关键作用。许多两亲性肽能够调节膜曲率，但关于指导曲率变化的特定结构因素的信息很少。 Epsin-1 是一种代表性蛋白质，被认为在网格蛋白包被的囊泡形成时启动质膜内陷。其 N 端螺旋段 (EpN18) 在诱导正膜曲率方面发挥着关键作用。本研究旨在阐明 EpN18 的基本结构特征，以便更好地理解一般曲率诱导机制，并设计合理控制膜曲率的有效工具。对 EpN18 衍生肽的结构剖析揭示了疏水性残基对 (i) 增强膜相互作用、(ii) 螺旋结构、(iii) 诱导正膜曲率和 (iv) 松弛脂质堆积的决定性贡献。通过用亮氨酸残基取代获得了最强的效果，因为这种 EpN18 类似物显示出促进八精氨酸细胞穿透肽流入活细胞的显着能力。
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.