美国华盛顿大学David Baker研究组开发出通过程序化对称破缺设计的四组分蛋白质纳米笼。相关论文于2024年12月18日在线发表在《自然》杂志上。

研究人员描述了一种通用的设计策略，通过三聚体构建单元的伪对称化，从规则的多面体出发，构建更高三角化数的架构。

电子显微镜确认了T=4纳米笼的结构，这些笼子具有48个（四面体）、96个（八面体）和240个（二十面体）亚单位，每个笼子有4条不同的链和6种不同的蛋白质-蛋白质界面，直径分别为33纳米、43纳米和75纳米。具有更高三角化数的病毒具备非常复杂的功能性。

该通用路径构建出更高三角化数的纳米笼，应该能够同样支持下一代多抗原展示疫苗候选物和靶向递送载体的开发。

据介绍，四个、八个或二十个C3对称蛋白质三聚体可以通过四面体、八面体或二十面体点群对称排列，生成封闭的笼状结构。病毒通过破坏完美的点群对称性，获得了更复杂的更高三角化数的二十面体结构。然而，自然界似乎并未探索类似的对称性破缺，用于四面体或八面体对称性。

附：英文原文

Title: Four-component protein nanocages designed by programmed symmetry breaking

Author: Lee, Sangmin, Kibler, Ryan D., Ahn, Green, Hsia, Yang, Borst, Andrew J., Philomin, Annika, Kennedy, Madison A., Huang, Buwei, Stoddard, Barry, Baker, David

Issue&Volume: 2024-12-18

Abstract: Four, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral, octahedral or icosahedral point group symmetry to generate closed cage-like structures1,2. Viruses access more complex higher triangulation number icosahedral architectures by breaking perfect point group symmetry3,4,5,6,7,8,9, but nature appears not to have explored similar symmetry breaking for tetrahedral or octahedral symmetries. Here we describe a general design strategy for building higher triangulation number architectures starting from regular polyhedra through pseudosymmetrization of trimeric building blocks. Electron microscopy confirms the structures of T=4 cages with 48 (tetrahedral), 96 (octahedral) and 240 (icosahedral) subunits, each with 4 distinct chains and 6 different protein–protein interfaces, and diameters of 33nm, 43nm and 75nm, respectively. Higher triangulation number viruses possess very sophisticated functionalities; our general route to higher triangulation number nanocages should similarly enable a next generation of multiple antigen-displaying vaccine candidates10,11 and targeted delivery vehicles12,13.

DOI: 10.1038/s41586-024-07814-1

Source: https://www.nature.com/articles/s41586-024-07814-1