Van 't Hoff Laboratory for Physical and Colloid Chemistry, Debye Institute for NanoMaterials Science, Utrecht University, Utrecht, The Netherlands.
Biophys J. 2012 Jun 20;102(12):2845-55. doi: 10.1016/j.bpj.2012.05.007. Epub 2012 Jun 19.
We put forward a modified Zipper model inspired by the statics and dynamics of the spontaneous reconstitution of rodlike tobacco mosaic virus particles in solutions containing the coat protein and the single-stranded RNA of the virus. An important ingredient of our model is an allosteric switch associated with the binding of the first protein unit to the origin-of-assembly domain of the viral RNA. The subsequent addition and conformational switching of coat proteins to the growing capsid we believe is catalyzed by the presence of the helical arrangement of bound proteins to the RNA. The model explains why the formation of complete viruses is favored over incomplete ones, even though the process is quasi-one-dimensional in character. We numerically solve the relevant kinetic equations and show that time evolution is different for the assembly and disassembly of the virus, the former exhibiting a time lag even if all forward rate constants are equal. We find the late-stage assembly kinetics in the presence of excess protein to be governed by a single-exponential relaxation, which agrees with available experimental data on TMV reconstruction.
我们提出了一个改进的 Zipper 模型，该模型受到溶液中杆状烟草花叶病毒颗粒自发重组的静态和动态的启发，其中包含外壳蛋白和病毒的单链 RNA。我们模型的一个重要组成部分是与第一个蛋白质单元与病毒 RNA 的组装原点域结合相关的变构开关。我们认为，随后的外壳蛋白的添加和构象转换到生长的衣壳是由结合到 RNA 的螺旋排列的存在催化的。该模型解释了为什么即使过程在性质上是准一维的，完整病毒的形成也比不完整病毒更有利。我们数值求解了相关的动力学方程，并表明病毒的组装和拆卸的时间演化是不同的，即使所有正向速率常数都相等，前者也表现出时间滞后。我们发现，在存在过量蛋白质的情况下，晚期组装动力学受单指数弛豫控制，这与 TMV 重建的可用实验数据一致。
