Mechanical elasticity as a physical signature of conformational dynamics in a virus particle
Mechanical elasticity as a physical signature of conformational dynamics in a virus particle
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DOI：
10.1073/pnas.1207437109
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发表时间：
2012-07-24
影响因子：
11.1
通讯作者：
Mateu, Mauricio G.
中科院分区：
文献类型：
--
作者：
Castellanos, Milagros;Perez, Rebeca;Mateu, Mauricio G.
在这项研究中，我们测试的假设，在病毒颗粒（或大的生物分子复合物）的机械弹性区域必须符合构象动态区域，因为这两个属性是内在相关的。通过使用小鼠衣壳微小病毒的19种变体对假设推导的预测进行验证。这些变体中的结构修饰减少、保留或恢复了衣壳孔周围区域的构象动力学，所述衣壳孔参与病毒感染性所需的分子易位事件。通过原子力显微镜分析了改性衣壳的机械弹性，结果证实了测试的每一个预测：任何损害孔区域构象重排的突变（或化学交联）都会增加它们的机械刚度。相反，任何保持孔隙区域动力学的突变也保持了它们的弹性。此外，恢复孔隙区域的动力学（通过先前的突变丢失）的任何伪回复也恢复了它们的弹性。最后，没有观察到其他衣壳区域的孔区域和机械弹性的动态之间的相关性。本研究（i）证实了病毒颗粒中局部机械弹性和构象动力学具有内在相关性的假设;（ii）提出通过原子力显微镜测定局部机械弹性，结合突变分析，可以用于识别和研究病毒颗粒和大生物分子复合物中的构象动力学区域;（iii）支持病毒中机械性质和生物功能之间的联系;（iv）表明病毒衣壳可以通过蛋白质工程用于纳米技术应用而大大硬化。
In this study we test the hypothesis that mechanically elastic regions in a virus particle (or large biomolecular complex) must coincide with conformationally dynamic regions, because both properties are intrinsically correlated. Hypothesis-derived predictions were subjected to verification by using 19 variants of the minute virus of mice capsid. The structural modifications in these variants reduced, preserved, or restored the conformational dynamism of regions surrounding capsid pores that are involved in molecular translocation events required for virus infectivity. The mechanical elasticity of the modified capsids was analyzed by atomic force microscopy, and the results corroborated every prediction tested: Any mutation (or chemical cross-linking) that impaired a conformational rearrangement of the pore regions increased their mechanical stiffness. On the contrary, any mutation that preserved the dynamics of the pore regions also preserved their elasticity. Moreover, any pseudo-reversion that restored the dynamics of the pore regions (lost through previous mutation) also restored their elasticity. Finally, no correlation was observed between dynamics of the pore regions and mechanical elasticity of other capsid regions. This study (i) corroborates the hypothesis that local mechanical elasticity and conformational dynamics in a viral particle are intrinsically correlated; (ii) proposes that determination by atomic force microscopy of local mechanical elasticity, combined with mutational analysis, may be used to identify and study conformationally dynamic regions in virus particles and large biomolecular complexes; (iii) supports a connection between mechanical properties and biological function in a virus; (iv) shows that viral capsids can be greatly stiffened by protein engineering for nanotechnological applications.