Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2120799119. doi: 10.1073/pnas.2120799119. Epub 2022 Mar 25.
SignificanceA large subclass of biomolecular condensates are linked to RNA regulation and are known as ribonucleoprotein (RNP) bodies. While extensive work has identified driving forces for biomolecular condensate formation, relatively little is known about forces that oppose assembly. Here, using a fungal RNP protein, Whi3, we show that a portion of its intrinsically disordered, glutamine-rich region modulates phase separation by forming transient alpha helical structures that promote the assembly of dilute phase oligomers. These oligomers detour Whi3 proteins from condensates, thereby impacting the driving forces for phase separation, the protein-to-RNA ratio in condensates, and the material properties of condensates. Our findings show how nanoscale conformational and oligomerization equilibria can influence mesoscale phase equilibria.
意义大量的生物分子凝聚物亚类与 RNA 调节有关，被称为核糖核蛋白 (RNP) 体。虽然已经有大量的工作确定了生物分子凝聚形成的驱动力，但相对而言，对抗组装的力知之甚少。在这里，我们使用真菌 RNP 蛋白 Whi3 表明，其部分固有无序、富含谷氨酰胺的区域通过形成促进稀相寡聚物组装的瞬时α螺旋结构来调节相分离。这些寡聚物使 Whi3 蛋白避开凝聚物，从而影响相分离的驱动力、凝聚物中的蛋白与 RNA 比以及凝聚物的材料特性。我们的研究结果表明纳米级构象和寡聚平衡如何影响介观相平衡。
