Curvature Engineering: Positive Membrane Curvature Induced by Epsin N-Terminal Peptide Boosts Internalization of Octaarginine

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• 作者：S铆lvia Pujals ; Hiroki Miyamae ; Sergii Afonin ; Tomo Murayama ; Hisaaki Hirose ; Ikuhiko Nakase ; Kentaro Taniuchi ; Masato Umeda ; Kazutami Sakamoto ; Anne S. Ulrich ; Shiroh Futaki
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：September 20, 2013
• 年：2013
• 卷：8
• 期：9
• 页码：1894-1899
• 全文大小：353K
• 年卷期：v.8,no.9(September 20, 2013)
• ISSN：1554-8937

文摘

Epsin-1 is a representative protein for inducing the positive curvature necessary for the formation of clathrin-coated pits. Here we demonstrate that the N-terminus 18-residue peptide of epsin-1 (EpN18) has this ability per se, as proved by differential scanning calorimetry (DSC) and solid-state NMR. Moreover, it is shown how this positive curvature promotion can be exploited for promoting the direct penetration of a representative cell-penetrating peptide (CPP), octaarginine (R₈), through artificial and plasma membranes. This synergistic effect has been used for the efficient delivery of a proapoptotic domain peptide (PAD), which induced high level of apoptosis only when coadministered with R₈ and EpN18, thus emphasizing the importance of positive curvature induction for achieving the desired ultimate cargo bioavailability.