美国得克萨斯农工大学Mittal Jeetain团队拓展了蛋白质液-液相分离的分子语言。相关研究成果于2024年3月29日发表于国际一流学术期刊《自然—化学》。

了解多肽序列与其相分离之间的关系对分析细胞功能、治疗疾病和设计新型生物材料具有重要意义。一些序列特征已被确定为蛋白质液相分离（LLPS）的驱动因素，被示意为LLPS的“分子语法”。

该文中，研究人员针对文献中以前忽略的序列特征进一步探讨了，序列如何调节相分离和所得缩合物的材料性质。研究人员制备重复多肽的序列变体，该序列变体没有带电荷的残基、高净电荷、没有甘氨酸残基或没有芳香或精氨酸残基。12个变体中除一个外，所有变体都表现出LLPS，尽管在组成上存在显著差异，但程度不同。

此外，发现所有形成的冷凝物都表现得像粘性流体，尽管它们的粘度差异很大。研究结果支持了协同工作以驱动冷凝物的相分离和动力学的，不同残基对（而不仅仅是少数残基）之间的多重相互作用模型。

附：英文原文

Title: Expanding the molecular language of protein liquid–liquid phase separation

Author: Rekhi, Shiv, Garcia, Cristobal Garcia, Barai, Mayur, Rizuan, Azamat, Schuster, Benjamin S., Kiick, Kristi L., Mittal, Jeetain

Issue&Volume: 2024-03-29

Abstract: Understanding the relationship between a polypeptide sequence and its phase separation has important implications for analysing cellular function, treating disease and designing novel biomaterials. Several sequence features have been identified as drivers for protein liquid–liquid phase separation (LLPS), schematized as a ‘molecular grammar’ for LLPS. Here we further probe how sequence modulates phase separation and the material properties of the resulting condensates, targeting sequence features previously overlooked in the literature. We generate sequence variants of a repeat polypeptide with either no charged residues, high net charge, no glycine residues or devoid of aromatic or arginine residues. All but one of 12 variants exhibited LLPS, albeit to different extents, despite substantial differences in composition. Furthermore, we find that all the condensates formed behaved like viscous fluids, despite large differences in their viscosities. Our results support the model of multiple interactions between diverse residue pairs—not just a handful of residues—working in tandem to drive the phase separation and dynamics of condensates.

DOI: 10.1038/s41557-024-01489-x

Source: https://www.nature.com/articles/s41557-024-01489-x