德国马克斯普朗克研究所教授Bonn, Mischa团队报道疏水相互作用驱动无序FUS LC的原纤维形成和有序化。相关研究成果发表在2023年5月25日出版的国际知名学术期刊《自然—化学》。
生物分子缩合物是富含蛋白质和动态的无膜细胞器，在一系列亚细胞过程中发挥着关键作用，包括膜运输和转录调控。然而，生物分子缩合物中固有无序蛋白质的异常相变可能导致形成与神经退行性疾病有关的不可逆原纤维和聚集体。尽管有这些影响，但这种转变背后的相互作用仍然模糊不清。
该文中，研究人员通过研究空气/水界面上无序的“融合肉瘤”（FUS）蛋白的低复杂性结构域来研究疏水相互作用的作用。使用表面特异性显微镜和光谱技术，发现疏水界面驱动原纤维的形成和FUS的分子有序化，从而形成类固体膜。这种相变发生在比标准FUS低复杂度液滴体形成所需的FUS浓度低600倍的情况下。这些观察结果突出了疏水效应对蛋白质相分离的重要性，并表明界面性质驱动不同的蛋白质相分离结构。
附：英文原文
Title: Fibril formation and ordering of disordered FUS LC driven by hydrophobic interactions
Author: Maltseva, Daria, Chatterjee, Sayantan, Yu, Chun-Chieh, Brzezinski, Mateusz, Nagata, Yuki, Gonella, Grazia, Murthy, Anastasia C., Stachowiak, Jeanne C., Fawzi, Nicolas L., Parekh, Sapun H., Bonn, Mischa
Issue&Volume: 2023-05-25
Abstract: Biomolecular condensates, protein-rich and dynamic membrane-less organelles, play critical roles in a range of subcellular processes, including membrane trafficking and transcriptional regulation. However, aberrant phase transitions of intrinsically disordered proteins in biomolecular condensates can lead to the formation of irreversible fibrils and aggregates that are linked to neurodegenerative diseases. Despite the implications, the interactions underlying such transitions remain obscure. Here we investigate the role of hydrophobic interactions by studying the low-complexity domain of the disordered ‘fused in sarcoma’ (FUS) protein at the air/water interface. Using surface-specific microscopic and spectroscopic techniques, we find that a hydrophobic interface drives fibril formation and molecular ordering of FUS, resulting in solid-like film formation. This phase transition occurs at 600-fold lower FUS concentration than required for the canonical FUS low-complexity liquid droplet formation in bulk. These observations highlight the importance of hydrophobic effects for protein phase separation and suggest that interfacial properties drive distinct protein phase-separated structures.
DOI: 10.1038/s41557-023-01221-1
Source: https://www.nature.com/articles/s41557-023-01221-1