title: Formation of size-controlled, denaturation-resistant lipid nanodiscs by an amphiphilic self-polymerizing peptide.
abstract: Nanodiscs are discoidal particles with a planar phospholipid bilayer enwrapped by proteins such as apolipoprotein A-I. Nanodiscs have been widely used for analyzing structures and functions of membrane proteins by dispersing them in solution. They are expected to be used as drug carriers and therapeutic agents. Amphiphilic peptides are known to form nanodiscs. However, the lipid-peptide nanodiscs are relatively unstable in solution, making them unsuitable for many applications. Here, we report the synthesis of an amphiphilic self-polymerizing peptide termed ASPP1, which polymerizes by intermolecular native chemical ligation reactions. ASPP1 spontaneously formed nanodiscs when added to phospholipid vesicles without using detergents. The diameter of the planar lipid bilayer in the nanodiscs was controlled by the lipid:peptide molar ratio. ASPP1-nanodiscs exhibited greater stability at high temperatures or in the presence of urea than nanodiscs formed by the non-polymerizing amphiphilic peptide or apolipoprotein A-I. Average and maximal degrees of ASPP1 polymerization were 2.4 and 12, respectively. Self-polymerization of the peptide appears to be responsible for stabilization of the nanodiscs. Our results open a new avenue for the development of nanodisc technology.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: kikeda@pha.u-toyama.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakano
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D058105:Polymerization; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D011489:Protein Denaturation; D012996:Solutions
chemical_list: D016632:Apolipoprotein A-I; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010743:Phospholipids; D011108:Polymers; D012996:Solutions
keywords: Amphiphilic peptide; Nanoparticle; Native chemical ligation; Phosphatidylcholine; Self-assembly