Landreh Michael, Osterholz Hannah, Chen Gefei, Knight Stefan D, Rising Anna, Leppert Axel
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
Commun Chem. 2024 Nov 12;7(1):260. doi: 10.1038/s42004-024-01357-2.
Liquid-liquid phase separation (LLPS) of proteins can be considered an intermediate solubility regime between disperse solutions and solid fibers. While LLPS has been described for several pathogenic amyloids, recent evidence suggests that it is similarly relevant for functional amyloids. Here, we review the evidence that links spider silk proteins (spidroins) and LLPS and its role in the spinning process. Major ampullate spidroins undergo LLPS mediated by stickers and spacers in their repeat regions. During spinning, the spidroins droplets shift from liquid to crystalline states. Shear force, altered ion composition, and pH changes cause micelle-like spidroin assemblies to form an increasingly ordered liquid-crystalline phase. Interactions between polyalanine regions in the repeat regions ultimately yield the characteristic β-crystalline structure of mature dragline silk fibers. Based on these findings, we hypothesize that liquid-liquid crystalline phase separation (LLCPS) can describe the molecular and macroscopic features of the phase transitions of major ampullate spidroins during spinning and speculate whether other silk types may use a similar mechanism to convert from liquid dope to solid fiber.
蛋白质的液-液相分离（LLPS）可被视为介于分散溶液和固体纤维之间的一种中间溶解状态。虽然已有研究描述了几种致病性淀粉样蛋白的液-液相分离现象，但最近的证据表明，其对于功能性淀粉样蛋白同样具有重要意义。在此，我们综述了将蜘蛛丝蛋白（蛛丝蛋白）与液-液相分离联系起来的证据及其在纺丝过程中的作用。主要壶腹蛛丝蛋白在其重复区域中由粘性区域和间隔区域介导发生液-液相分离。在纺丝过程中，蛛丝蛋白液滴从液态转变为晶态。剪切力、离子组成的改变以及pH值变化会促使胶束状的蛛丝蛋白聚集体形成越来越有序的液晶相。重复区域中聚丙氨酸区域之间的相互作用最终产生了成熟拖牵丝纤维特有的β-晶态结构。基于这些发现，我们推测液-液晶相分离（LLCPS）可以描述主要壶腹蛛丝蛋白在纺丝过程中相变的分子和宏观特征，并推测其他类型的蛛丝是否可能采用类似机制从液态原液转变为固态纤维。
