Center for Biological Systems Engineering, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, United States.
Department of Biophysics, Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, United States.
Elife. 2017 Nov 1;6:e30294. doi: 10.7554/eLife.30294.
Phase transitions of linear multivalent proteins control the reversible formation of many intracellular membraneless bodies. Specific non-covalent crosslinks involving domains/motifs lead to system-spanning networks referred to as gels. Gelation transitions can occur with or without phase separation. In gelation driven by phase separation multivalent proteins and their ligands condense into dense droplets, and gels form within droplets. System spanning networks can also form without a condensation or demixing of proteins into droplets. Gelation driven by phase separation requires lower protein concentrations, and seems to be the biologically preferred mechanism for forming membraneless bodies. Here, we use coarse-grained computer simulations and the theory of associative polymers to uncover the physical properties of intrinsically disordered linkers that determine the extent to which gelation of linear multivalent proteins is driven by phase separation. Our findings are relevant for understanding how sequence-encoded information in disordered linkers influences phase transitions of multivalent proteins.
线性多价蛋白的相转变控制着许多细胞无膜结构的形成。涉及结构域/基序的特定非共价交联导致了被称为凝胶的系统跨越网络。凝胶化转变可以在有或没有相分离的情况下发生。在由相分离驱动的凝胶化中，多价蛋白及其配体凝聚成密集的液滴，并且凝胶在液滴内形成。系统跨越网络也可以在没有蛋白质凝聚或分相成液滴的情况下形成。由相分离驱动的凝胶化需要较低的蛋白质浓度，并且似乎是形成无膜结构的首选机制。在这里，我们使用粗粒化计算机模拟和缔合聚合物理论来揭示决定线性多价蛋白凝胶化由相分离驱动程度的内在无序连接物的物理性质。我们的发现对于理解无序连接物中序列编码信息如何影响多价蛋白的相变具有重要意义。
