A Selection for Assembly Reveals That a Single Amino Acid Mutant of the Bacteriophage MS2 Coat Protein Forms a Smaller Virus-like Particle
A Selection for Assembly Reveals That a Single Amino Acid Mutant of the Bacteriophage MS2 Coat Protein Forms a Smaller Virus-like Particle
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DOI：
10.1021/acs.nanolett.6b02948
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发表时间：
2016-09-01
期刊：
影响因子：
10.8
通讯作者：
Tullman-Ercek, Danielle
中科院分区：
文献类型：
--
作者：
Asensio, Michael A.;Morella, Norma M.;Tullman-Ercek, Danielle
病毒样颗粒用于封装药物、显像剂、酶和其他生物活性分子，以增强其功能。然而，大多数病毒样颗粒的尺寸不灵活，妨碍了针对不同应用设计适当尺寸的容器。在这里，我们描述了病毒样颗粒组装的色谱选择。通过这种选择，我们确定了噬菌体 MS2 外壳蛋白的单个氨基酸取代，它介导颗粒几何形状从 T = 3 到 T = 1 二十面体对称性的均匀转换。由此产生的较小颗粒保留了在体外分解和重新组装的能力，以及经过化学修饰以将货物装载到其内部空腔中的能力。这对 27 和 17 nm MS2 颗粒将允许直接检查尺寸对病毒样颗粒已建立的应用（包括药物递送和成像）中功能的影响。
Virus-like particles are used to encapsulate drugs, imaging agents, enzymes, and other biologically active molecules in order to enhance their function. However, the size of most virus-like particles is inflexible, precluding the design of appropriately sized containers for different applications. Here, we describe a chromatographic selection for virus-like particle assembly. Using this selection, we identified a single amino acid substitution to the,coat protein of bacteriophage MS2 that mediates a uniform switch in particle geometry from T = 3 to T = 1 icosahedral symmetry. The resulting smaller particle retains the ability to be disassembled and reassembled in vitro and to be chemically modified to load cargo into its interior cavity. The pair of 27 and 17 nm MS2 particles will allow,direct examination of the effect of size on function in established applications of virus-like particles, including drug:delivery and imaging.