Kalapothakis Jason M D, Morris Ryan J, Szavits-Nossan Juraj, Eden Kym, Covill Sam, Tabor Sean, Gillam Jay, Barran Perdita E, Allen Rosalind J, MacPhee Cait E
School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK; School of Chemistry, University of Edinburgh, Edinburgh, UK.
School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
Biophys J. 2015 May 5;108(9):2300-11. doi: 10.1016/j.bpj.2015.03.021.
The ability to control the morphologies of biomolecular aggregates is a central objective in the study of self-assembly processes. The development of predictive models offers the surest route for gaining such control. Under the right conditions, proteins will self-assemble into fibers that may rearrange themselves even further to form diverse structures, including the formation of closed loops. In this study, chicken egg white ovalbumin is used as a model for the study of fibril loops. By monitoring the kinetics of self-assembly, we demonstrate that loop formation is a consequence of end-to-end association between protein fibrils. A model of fibril formation kinetics, including end-joining, is developed and solved, showing that end-joining has a distinct effect on the growth of fibrillar mass density (which can be measured experimentally), establishing a link between self-assembly kinetics and the underlying growth mechanism. These results will enable experimentalists to infer fibrillar morphologies from an appropriate analysis of self-assembly kinetic data.
控制生物分子聚集体的形态是自组装过程研究的核心目标。预测模型的发展为实现这种控制提供了最可靠的途径。在适当条件下，蛋白质会自组装成纤维，这些纤维甚至可能进一步重新排列形成各种结构，包括闭环的形成。在本研究中，鸡卵清蛋白被用作研究纤维环的模型。通过监测自组装动力学，我们证明环的形成是蛋白质纤维之间端对端缔合的结果。我们开发并求解了一个包括末端连接的纤维形成动力学模型，结果表明末端连接对纤维质量密度的增长有显著影响（这可以通过实验测量），从而建立了自组装动力学与潜在生长机制之间的联系。这些结果将使实验人员能够通过对自组装动力学数据的适当分析推断出纤维形态。
