Evolution of interface binding strengths in simplified model of protein quaternary structure
Evolution of interface binding strengths in simplified model of protein quaternary structure
复制标题
DOI：
10.1371/journal.pcbi.1006886
复制
发表时间：
2019-06-01
影响因子：
4.3
通讯作者：
Ahnert, Sebastian E.
中科院分区：
文献类型：
--
作者：
Leonard, Alexander S.;Ahnert, Sebastian E.
蛋白质自组装成蛋白质四级结构对许多生物过程至关重要，而蛋白质错误组装是多种蛋白质病的病因。近年来，蛋白质自组装的抽象晶格模型已被用于模拟蛋白质四级结构的演化和组装，并为研究此类系统的基因型 - 表型图谱提供了一种可行的方法。在此，我们通过将界面表示为可变的二进制字符串来对这些模型进行推广。这一简单的改变使我们能够对界面强度、界面对称性和确定性组装途径的演化进行建模。利用推广后的模型，我们能够重现针对真实蛋白质复合物所确立的两个重要结果：第一个是蛋白质组装途径处于进化选择之下，以最大程度减少错误组装。第二个是复合物的组装途径反映其进化历史，并且两者都可从界面的相对强度推导得出。这些结果表明，推广后的晶格模型提供了一个强大的新型理想化框架，有助于研究蛋白质自组装过程及其演化。
作者总结：蛋白质复合物通过相互作用的结合位点将单个蛋白质连接在一起进行组装。由于生物进化的时间尺度很长，可能很难重建这些相互作用是如何随时间变化的。我们使用蛋白质的简化表示在计算机上模拟这些复合物的演化。在某些情况下，复合物组装的顺序至关重要。我们表明，生物进化会增强必须更早发生的相互作用的强度，并降低后续相互作用的强度。关于相互作用倾向于更强或更弱的类似知识也有助于预测复合物的进化起源。虽然这些模拟过于理想化，无法做出精确的预测，但组装中的有序途径与进化之间的这种一般联系与在真实蛋白质复合物中已确立的观察结果非常吻合。这意味着我们的模型提供了一个强大的框架，有助于研究蛋白质复合物的组装和进化。
The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new idealized framework to facilitate the study of protein self-assembly processes and their evolution.Author summary Protein complexes assemble by joining individual proteins together through interacting binding sites. Because of the long time scales of biological evolution, it can be difficult to reconstruct how these interactions change over time. We use simplified representations of proteins to simulate the evolution of these complexes on a computer. In some cases the order in which the complex assembles is crucial. We show that biological evolution increases the strength of interactions that must occur earlier, and decreases the strength of later interactions. Similar knowledge of interactions being preferred to be stronger or weaker can also help to predict the evolutionary ancestry of a complex. While these simulations are too idealized to make exact predictions, this general link between ordered pathways in assembly and evolution matches well-established observations that have been made in real protein complexes. This means that our model provides a powerful framework to help study protein complex assembly and evolution.