在拥挤环境中构建蛋白质超大复合物的物理原理
Physical principles of building protein megacomplexes in a crowded milieu
AI总结：
研究通过统计物理框架揭示了在拥挤环境中蛋白质超大复合物组装的物理机制，发现发散蛋白质通过排除体积作用协调组装，为理解细胞结构提供了新视角。
摘要：
多种由同一基因组产生的蛋白质表型表达代表了蛋白质相对丰度及其配比的变化。缺乏确定的组成部分挑战了蛋白质超大复合物和细胞结构的建模。尽管在蛋白质结构预测方面取得了进展，但蛋白质相互作用的机制以及它们组装的超大复合物的形成仍不清楚。在这里，我们提出了一种统计物理学的大正则系综框架，利用观测到的质量光谱数据集，包括蛋白质相对丰度和交叉连接连接，来探索驱动超大复合物形成相互作用的蛋白质相互作用。以染色质重塑器超大复合物INO80为例，我们发现了一类发散的蛋白质，在依赖于其他蛋白质排除体积的情况下，起着在最近邻之外协调组装的关键作用。在排除体积由变化的拥挤含量约束下，这些发散的亚基通过选择性成分形成簇，逐渐发展成构型不同的结构。我们提出了INO80染色质重塑器复合物的机器观点，其中每个松散结合的亚基可以偶尔被招募作为部件加入到核心组装中，由排除体积驱动。我们的计算框架为将大分子拥挤作为必要的物理化学变量，代表细胞状态，重新配置蛋白质超大复合物的结构提供了机制见解。
英文摘要：
Multiple phenotypic protein expressions arising from one genome represent variations in the protein relative abundance and their stoichiometry. A lack of definite compositional parts challenges the modeling of protein megacomplexes and cellular architectures. Despite the advances in protein structural predictions with AI, the mechanism of protein interactions and the emergence of megacomplexes they assemble remains unclear. Here, we present a statistical physics framework of grand canonical ensemble to explore the protein interactions that drive the emergent assembly of a megacomplex using the observational mass spectrometry datasets including protein relative abundance and the cross linked connections. Using chromatin remodeler megacomplex, INO80, as an example, we discovered a class of divergent protein that plays a critical role in orchestrating the assembly beyond nearest neighbors, dependent on the excluded volumes exerted by others. With the constraints of the excluded volumes by varying crowding contents, these divergent subunits orchestrate and form clusters with selective components growing into configurationally distinct architectures. We propose a machinery view for the INO80 chromatin remodeler complex where each loosely associated subunits can be occasionally recruited for parts as attachment into a core assembly driven by excluded volumes. Our computational framework provides a mechanistic insight into taking the macromolecular crowding as necessary physicochemical variables representing cell states to remodel the configurations of protein megacomplexes with structurally loose modules.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
