Manipulation of the mechanical properties of a virus by protein engineering
Manipulation of the mechanical properties of a virus by protein engineering
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DOI：
10.1073/pnas.0708017105
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发表时间：
2008-03-18
影响因子：
11.1
通讯作者：
Mateu, Mauricio G.
中科院分区：
文献类型：
--
作者：
Carrasco, Carolina;Castellanos, Milagros;Mateu, Mauricio G.
在之前的研究中，我们发现球形病毒（小鼠的微小病毒）中的DNA分子通过各向异性地增加病毒的机械刚度来发挥建筑作用。有限元模型预测，这种机械强化是晶体学上可见的短DNA补丁和内衣壳壁之间相互作用的结果。我们现在已经通过使用蛋白质工程测试了这个模型。选定的氨基酸侧链已被截短，以特异性地去除衣壳和可见的DNA补丁之间的主要相互作用，并且已使用原子力显微镜测量了突变对病毒颗粒刚度的影响。突变不影响空衣壳的刚度;然而，它们显著降低了DNA填充的病毒体和空衣壳之间的刚度差异。结果（i）揭示了单个化学基团之间的分子间相互作用有助于超分子组装的机械性质，并且（ii）将特定的蛋白质-DNA相互作用确定为病毒刚性各向异性增加的起源。这项研究还表明，它是可能的，以控制蛋白质纳米粒子的机械性能的基础上的力学模型的蛋白质工程的合理应用。
In a previous study, we showed that the DNA molecule within a spherical virus (the minute virus of mice) plays an architectural role by anisotropically increasing the mechanical stiffness of the virus. A finite element model predicted that this mechanical reinforcement is a consequence of the interaction between crystallographically visible, short DNA patches and the inner capsid wall. We have now tested this model by using protein engineering. Selected amino acid side chains have been truncated to specifically remove major interactions between the capsid and the visible DNA patches, and the effect of the mutations on the stiffness of virus particles has been measured using atomic force microscopy. The mutations do not affect the stiffness of the empty capsid; however, they significantly reduce the difference in stiffness between the DNA-filled virion and the empty capsid. The results (i) reveal that intermolecular interactions between individual chemical groups contribute to the mechanical properties of a supramolecular assembly and (it) identify specific protein-DNA interactions as the origin of the anisotropic increase in the rigidity of a virus. This study also demonstrates that it is possible to control the mechanical properties of a protein nanoparticle by the rational application of protein engineering based on a mechanical model.