Laboratoire de Biophysique Moléculaire aux Interfaces, Gembloux Agro-Bio Tech, University of Liège, Passage des déportés 2, 5030 Gembloux, Belgium.
Institut des Sciences de la Vie, Université catholique de Louvain, 4-5 Place Croix du Sud, 1348 Louvain-la-Neuve, Belgium.
Int J Mol Sci. 2018 Sep 14;19(9):2772. doi: 10.3390/ijms19092772.
By manipulating the various physicochemical properties of amino acids, the design of peptides with specific self-assembling properties has been emerging for more than a decade. In this context, short peptides possessing detergent properties (so-called "peptergents") have been developed to self-assemble into well-ordered nanostructures that can stabilize membrane proteins for crystallization. In this study, the peptide with "peptergency" properties, called ADA8 and extensively described by Tao et al., is studied by molecular dynamic simulations for its self-assembling properties in different conditions. In water, it spontaneously forms beta sheets with a β barrel-like structure. We next simulated the interaction of this peptide with a membrane protein, the bacteriorhodopsin, in the presence or absence of a micelle of dodecylphosphocholine. According to the literature, the peptergent ADA8 is thought to generate a belt of β structures around the hydrophobic helical domain that could help stabilize purified membrane proteins. Molecular dynamic simulations are here used to image this mechanism and provide further molecular details for the replacement of detergent molecules around the protein. In addition, we generalized this behavior by designing an amphipathic peptide with beta propensity, which was called ABZ12. Both peptides are able to surround the membrane protein and displace surfactant molecules. To our best knowledge, this is the first molecular mechanism proposed for "peptergency".
通过操纵氨基酸的各种物理化学性质,具有特定自组装特性的肽的设计已经出现了十多年。在这种情况下,开发了具有去污剂特性(所谓的“peptergents”)的短肽,可自组装成有序的纳米结构,从而稳定用于结晶的膜蛋白。在这项研究中,研究了具有“peptergency”特性的肽,称为 ADA8,并由 Tao 等人进行了广泛描述,通过分子动力学模拟研究了其在不同条件下的自组装特性。在水中,它会自发形成具有 β 桶状结构的β片层。接下来,我们模拟了该肽与膜蛋白细菌视紫红质在存在或不存在十二烷基磷酸胆碱胶束的情况下的相互作用。根据文献,认为 peptergent ADA8 会在疏水性螺旋结构域周围产生一条 β 结构带,有助于稳定纯化的膜蛋白。分子动力学模拟用于模拟该机制,并为蛋白质周围去污剂分子的替代提供进一步的分子细节。此外,我们通过设计具有β倾向的两亲肽 ABZ12 来推广这种行为。这两种肽都能够包围膜蛋白并置换表面活性剂分子。据我们所知,这是首次提出用于“peptergency”的分子机制。