Roterman I, Słupina M, Dułak D, Konieczny L
Department of Bioinformatics and Telemedicine, Jagiellonian University Medical College, ul. Medyczna 7, Kraków 30-688, Poland.
ALSTOM ZWUS Sp. z o.o., Modelarska 12, Katowice 40-142, Poland.
Comput Struct Biotechnol J. 2025 Apr 13;27:1648-1659. doi: 10.1016/j.csbj.2025.04.016. eCollection 2025.
Analysis of the structure of proteins based on the evaluation of their geometric structure (secondary and supersecondary structure) can be extended to assess the structuring of the hydrophobic region of a protein. Such analysis of amyloid protein structures leads to the identification of three scenarios for amyloid formation. One is the loss of the micelle-like ordering present in the native form (a centric hydrophobic nucleus with a polar surface) in favour of a disordered distribution of hydrophobicity in the amyloid form. The term "micelle-like" is to be understood as specific hydrophobic burial. The second scenario is the reverse process, when the highly disordered distribution of hydrophobicity in the native form is replaced by a hydrophobic burial after amyloid transformation. These two scenarios have been identified for pathological (neurodegenerative) amyloids. The third scenario is the presence of hydrophobic burial ordering in a functional amyloid fibril. In this case, this ordering is present both in the fibril and in the single chain that is the building block of the fibril. This hydrophobic burial ordering provides a means of self-control of fibril size. It prevents unrestricted fibril propagation, which in the case of pathological amyloids is the main factor that disrupts the normal functioning of organelles in the amyloid surroundings. Population analysis (including numerous polymorphic forms) was performed using a collection of structures deposited in the Amyloid Atlas database. These observations allow the construction of a kind of amyloid funnel model, in which the energy minimum depends on external, environmental conditions that may be evaluated using the fuzzy oil drop model in its modified version (FOD-M).
基于对蛋白质几何结构（二级和超二级结构）评估的蛋白质结构分析可扩展至评估蛋白质疏水区域的结构。对淀粉样蛋白结构的此类分析可识别出淀粉样蛋白形成的三种情况。一种情况是天然形式（具有极性表面的中心疏水核）中存在的类似胶束的有序性丧失，转而在淀粉样形式中形成无序的疏水性分布。术语“类似胶束”应理解为特定的疏水埋藏。第二种情况是相反的过程，即天然形式中高度无序的疏水性分布在淀粉样蛋白转化后被疏水埋藏所取代。这两种情况已在病理性（神经退行性）淀粉样蛋白中得到确认。第三种情况是功能性淀粉样纤维中存在疏水埋藏有序性。在这种情况下，这种有序性存在于纤维中以及作为纤维构建块的单链中。这种疏水埋藏有序性提供了一种控制纤维大小的自我调节方式。它可防止纤维不受限制地生长，而在病理性淀粉样蛋白的情况下，不受限制的纤维生长是破坏淀粉样蛋白周围细胞器正常功能的主要因素。使用淀粉样蛋白图谱数据库中存储的结构集合进行了群体分析（包括众多多态形式）。这些观察结果有助于构建一种淀粉样蛋白漏斗模型，其中能量最小值取决于外部环境条件，可使用其改进版本的模糊油滴模型（FOD-M）对这些条件进行评估。
