Programmable polymorphism of a virus-like particle.
Programmable polymorphism of a virus-like particle.
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DOI：
10.1038/s43246-022-00229-3
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发表时间：
2022-02-07
影响因子：
7.8
通讯作者：
Heddle JG
中科院分区：
文献类型：
--
作者：
Biela AP;Naskalska A;Fatehi F;Twarock R;Heddle JG
病毒样颗粒(VLP)在人工疫苗和药物输送系统方面具有巨大的潜力。控制其大小的能力具有广泛的实用价值，但使用单个蛋白质亚基实现这种受控的多态性是具有挑战性的，因为它需要改变VLP的几何结构。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VLP的大小控制，以将形态转变为明显更大的形式。通过改变镶件的长度和类型来控制最终的VLP尺寸和几何图形。新的VLP的低温电子显微镜结构，结合它们的组装动力学模型，表明野生型(T=3)、T=4、D3和D5对称的VLP的丰度可以这样偏向。我们提出了一种机制，通过插入导致衣壳蛋白二聚体动态行为的改变，影响对称和不对称构象之间的相互转化，从而决定VLP的大小和形态。
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 (T = 3), T = 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.