Biela Artur P, Naskalska Antonina, Fatehi Farzad, Twarock Reidun, Heddle Jonathan G
Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-392 Krakow, Poland.
Departments of Mathematics, University of York, York YO10 5DD, UK.
Commun Mater. 2022 Feb 7;3:7. doi: 10.1038/s43246-022-00229-3.
Virus-like particles (VLPs) have significant potential as artificial vaccines and drug delivery systems. The ability to control their size has wide ranging utility but achieving such controlled polymorphism using a single protein subunit is challenging as it requires altering VLP geometry. Here we achieve size control of MS2 bacteriophage VLPs via insertion of amino acid sequences in an external loop to shift morphology to significantly larger forms. The resulting VLP size and geometry is controlled by altering the length and type of the insert. Cryo electron microscopy structures of the new VLPs, in combination with a kinetic model of their assembly, show that the abundance of wild type ( = 3), = 4, D3 and D5 symmetrical VLPs can be biased in this way. We propose a mechanism whereby the insert leads to a change in the dynamic behavior of the capsid protein dimer, affecting the interconversion between the symmetric and asymmetric conformers and thus determining VLP size and morphology.
病毒样颗粒（VLPs）作为人工疫苗和药物递送系统具有巨大潜力。控制其大小的能力具有广泛的用途，但使用单个蛋白质亚基实现这种可控的多态性具有挑战性，因为这需要改变VLP的几何形状。在这里，我们通过在外部环中插入氨基酸序列来实现MS2噬菌体VLPs的大小控制，从而将形态转变为明显更大的形式。所得VLP的大小和几何形状通过改变插入片段的长度和类型来控制。新VLPs的冷冻电子显微镜结构与其组装动力学模型相结合，表明野生型（ = 3）、 = 4、D3和D5对称VLPs的丰度可以通过这种方式得到偏向。我们提出了一种机制，即插入片段导致衣壳蛋白二聚体的动态行为发生变化，影响对称和不对称构象体之间的相互转化，从而决定VLP的大小和形态。
