理想原纤维形成的一般方面的建模
Modeling generic aspects of ideal fibril formation
摘要：
许多不同的蛋白质自聚集成不溶性原纤维，通过可逆添加基本构建块在顶端生长。但除了这个共同的原则，原纤维形成的方式是非常不同的，有各种中间形式，可以通过物理化学条件或氨基酸序列的微小修改进行重组。为了绕过这种复杂性，原纤维形成的多方面现象在这里被简化为针对原纤维的线性原型定义的最基本的原理。选定的通用功能，包括成核，伸长和构象招聘，建模使用最低限度的假设和工具，通过分离平衡动力学方面和在体外从体内条件。这些还原论的方法允许带出已知的和新的雏形，包括成核的动力学和平衡效应，成核的伸长的双重影响，成核和原纤维数量的动力学限制，以及通过从降解中拯救复合物在体内的积累。这些过程中被忽视的方面也指出：原纤维长度的指数分布可以使用各种模型，因为它是由于随机性只恢复。它也表明，同一术语“临界浓度”用于不同的事情，无论是涉及成核或伸长。
英文摘要：
Many different proteins self-aggregate into insoluble fibrils growing apically by reversible addition of elementary building blocks. But beyond this common principle, the modalities of fibril formation are very disparate, with various intermediate forms which can be reshuffled by minor modifications of physico-chemical conditions or amino-acid sequences. To bypass this complexity, the multifaceted phenomenon of fibril formation is reduced here to its most elementary principles defined for a linear prototype of fibril. Selected generic features, including nucleation, elongation and conformational recruitment, are modeled using minimalist hypotheses and tools, by separating equilibrium from kinetic aspects and in vitro from in vivo conditions. These reductionist approaches allow to bring out known and new rudiments, including the kinetic and equilibrium effects of nucleation, the dual influence of elongation on nucleation, the kinetic limitations on nucleation and fibril numbers and the accumulation of complexes in vivo by rescue from degradation. Overlooked aspects of these processes are also pointed: the exponential distribution of fibril lengths can be recovered using various models because it is attributable to randomness only. It is also suggested that the same term "critical concentration" is used for different things, involved in either nucleation or elongation.
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