Howard Hughes Medical Institute, Department of Neuroscience, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Nano Lett. 2020 Aug 12;20(8):6032-6037. doi: 10.1021/acs.nanolett.0c02048. Epub 2020 Jul 15.
Nanodiscs (ND) are soluble phospholipid bilayers bounded by membrane scaffold proteins; they have become invaluable in the study of membrane proteins. However, this multifunctional tool has been used individually, and applications involving multiple NDs and their interactions have fallen far behind their counterpart membrane model system: liposomes. One major obstacle is the lack of reliable methods to manage the spatial arrangement of NDs. Here we sought to extend the utility of NDs by organizing them on DNA origami. NDs constructed with DNA-anchor amphiphiles were placed precisely and specifically into these DNA nanostructures via hybridization. Four different tethering strategies were explored and validated. A variety of geometric patterns of NDs were successfully programmed on origami, as evidenced by electron microscopy. The ND ensembles generated in this study provide new and powerful platforms to study protein-lipid or protein-protein interactions with spatial control of membranes.
纳米盘（ND）是由膜支架蛋白包围的可溶磷脂双层；它们在膜蛋白研究中变得非常有价值。然而，这个多功能工具一直是单独使用的，涉及多个 ND 及其相互作用的应用远远落后于其对应的膜模型系统：脂质体。一个主要的障碍是缺乏可靠的方法来管理 ND 的空间排列。在这里，我们试图通过在 DNA 折纸结构上对其进行组织来扩展 ND 的用途。通过杂交，使用 DNA 锚定两亲分子构建的 ND 可以精确和特异性地放置在这些 DNA 纳米结构中。探索并验证了四种不同的系链策略。通过电子显微镜证实，成功地在折纸结构上对 ND 进行了各种几何图案的编程。本研究中产生的 ND 组合为研究具有膜空间控制的蛋白质-脂质或蛋白质-蛋白质相互作用提供了新的强大平台。
