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Switch from Polymorphic to Homogenous Self‐Assembly of Virus‐Like Particles of Simian Virus 40 through Double‐Cysteine Substitution
Small ( IF 13.0 ) Pub Date : 2020-10-15 , DOI: 10.1002/smll.202004484 Chengchen Xu 1, 2 , Weiwei Zhu 2, 3 , Hanjing Mao 2, 3 , Wenjing Zhang 2, 3 , Gen-Quan Yin 1 , Xian-En Zhang 4 , Feng Li 2
Small ( IF 13.0 ) Pub Date : 2020-10-15 , DOI: 10.1002/smll.202004484 Chengchen Xu 1, 2 , Weiwei Zhu 2, 3 , Hanjing Mao 2, 3 , Wenjing Zhang 2, 3 , Gen-Quan Yin 1 , Xian-En Zhang 4 , Feng Li 2
Affiliation
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Self‐assembled virus‐like particles (VLPs) hold great potential as natural nanomaterials for applications in many fields. For such purposes, monodisperse size distribution is a desirable property. However, the VLPs of simian virus 40 (SV40), a representative VLP platform, are characterized by polymorphism. In an attempt to eliminate the polymorphism, 15 mutants of the VLP subunit (VP1) are constructed through the substitution of double cysteines at the VP1 pentamer interfaces, generating a group of VLPs with altered size distributions. One of the mutants, SS2 (L102C/P300C), specifically forms homogenous T = 1‐like tiny VLPs of 24 ± 3 nm in diameter. Moreover, the stability of the SS2 VLPs is markedly enhanced compared with that of wild‐type VLPs. The homogeneous self‐assembly and stability enhancement of SS2 VLPs can be attributed to the new disulfide bonds contributed by Cys102 and Cys300, which are identified by mass spectrometry and explored by molecular dynamics simulations. Endocytosis inhibition assays indicate that SS2 VLPs, like the polymorphic wild‐type VLPs, preserve the multipathway feature of cellular uptake. SS2 VLPs may serve as an evolved version of SV40 VLPs in future studies and applications. The findings of this work would be useful for the design and fabrication of VLP‐based materials and devices.
中文翻译：
通过双半胱氨酸替代，从猿猴病毒40病毒样颗粒的多态自我组装转变为同质自我组装
自组装病毒样颗粒（VLP）作为天然纳米材料具有巨大的潜力，可用于许多领域。为此目的，单分散尺寸分布是理想的性能。但是，猿猴病毒40（SV40）的VLP（具有代表性的VLP平台）具有多态性。为了消除多态性，通过在VP1五聚体界面处双半胱氨酸的取代，构建了15个VLP亚基（VP1）突变体，从而产生了一组具有改变的大小分布的VLP。突变体之一SS2（L102C / P300C）特异性形成同源T =直径为24±3 nm的类似于1的微小VLP。此外，与野生型VLP相比，SS2 VLP的稳定性显着增强。SS2 VLP的均匀自组装和稳定性增强可以归因于Cys102和Cys300贡献的新的二硫键，它们通过质谱鉴定并通过分子动力学模拟进行了探索。胞吞抑制试验表明，SS2 VLP与多态性野生型VLP一样，保留了细胞摄取的多途径功能。SS2 VLP在将来的研究和应用中可以作为SV40 VLP的演进版本。这项工作的发现对于基于VLP的材料和设备的设计和制造非常有用。
更新日期：2020-11-12
中文翻译：
通过双半胱氨酸替代，从猿猴病毒40病毒样颗粒的多态自我组装转变为同质自我组装
自组装病毒样颗粒（VLP）作为天然纳米材料具有巨大的潜力，可用于许多领域。为此目的，单分散尺寸分布是理想的性能。但是，猿猴病毒40（SV40）的VLP（具有代表性的VLP平台）具有多态性。为了消除多态性，通过在VP1五聚体界面处双半胱氨酸的取代，构建了15个VLP亚基（VP1）突变体，从而产生了一组具有改变的大小分布的VLP。突变体之一SS2（L102C / P300C）特异性形成同源T =直径为24±3 nm的类似于1的微小VLP。此外，与野生型VLP相比，SS2 VLP的稳定性显着增强。SS2 VLP的均匀自组装和稳定性增强可以归因于Cys102和Cys300贡献的新的二硫键，它们通过质谱鉴定并通过分子动力学模拟进行了探索。胞吞抑制试验表明，SS2 VLP与多态性野生型VLP一样，保留了细胞摄取的多途径功能。SS2 VLP在将来的研究和应用中可以作为SV40 VLP的演进版本。这项工作的发现对于基于VLP的材料和设备的设计和制造非常有用。
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