Michaels Thomas C T, Yde Pernille, Willis Julian C W, Jensen Mogens H, Otzen Daniel, Dobson Christopher M, Buell Alexander K, Knowles Tuomas P J
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark.
J Chem Phys. 2015 Oct 28;143(16):164901. doi: 10.1063/1.4933230.
A number of different proteins possess the ability to polymerize into filamentous structures. Certain classes of such assemblies can have key functional roles in the cell, such as providing the structural basis for the cytoskeleton in the case of actin and tubulin, while others are implicated in the development of many pathological conditions, including Alzheimer's and Parkinson's diseases. In general, the fragmentation of such structures changes the total number of filament ends, which act as growth sites, and hence is a key feature of the dynamics of filamentous growth phenomena. In this paper, we present an analytical study of the master equation of breakable filament assembly and derive closed-form expressions for the time evolution of the filament length distribution for both open and closed systems with infinite and finite monomer supply, respectively. We use this theoretical framework to analyse experimental data for length distributions of insulin amyloid fibrils and show that our theory allows insights into the microscopic mechanisms of biofilament assembly to be obtained beyond those available from the conventional analysis of filament mass only.
许多不同的蛋白质具有聚合成丝状结构的能力。这类组装体的某些类别在细胞中可发挥关键的功能作用，比如肌动蛋白和微管蛋白为细胞骨架提供结构基础，而其他一些则与包括阿尔茨海默病和帕金森病在内的许多病理状况的发展有关。一般来说，此类结构的碎片化会改变作为生长位点的丝端总数，因此是丝状生长现象动力学的一个关键特征。在本文中，我们对可断裂丝组装的主方程进行了分析研究，并分别推导了无限和有限单体供应情况下开放和封闭系统中丝长度分布随时间演化的闭式表达式。我们利用这一理论框架分析胰岛素淀粉样纤维长度分布的实验数据，并表明我们的理论能够深入了解生物丝组装的微观机制，而这是仅从常规的丝质量分析中无法获得的。
