Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, USA; email:
Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, New York 11794, USA; email:
Annu Rev Phys Chem. 2020 Apr 20;71:53-75. doi: 10.1146/annurev-physchem-071819-113553.
Biological phase separation is known to be important for cellular organization, which has recently been extended to a new class of biomolecules that form liquid-like droplets coexisting with the surrounding cellular or extracellular environment. These droplets are termed membraneless organelles, as they lack a dividing lipid membrane, and are formed through liquid-liquid phase separation (LLPS). Elucidating the molecular determinants of phase separation is a critical challenge for the field, as we are still at the early stages of understanding how cells may promote and regulate functions that are driven by LLPS. In this review, we discuss the role that disorder, perturbations to molecular interactions resulting from sequence, posttranslational modifications, and various regulatory stimuli play on protein LLPS, with a particular focus on insights that may be obtained from simulation and theory. We finally discuss how these molecular driving forces alter multicomponent phase separation and selectivity.
生物相分离对于细胞组织非常重要，这种现象最近被扩展到一类新的生物分子，这些生物分子形成类似液体的液滴，与周围的细胞或细胞外环境共存。这些液滴被称为无膜细胞器，因为它们缺乏分隔脂质膜，并且通过液-液相分离（LLPS）形成。阐明相分离的分子决定因素是该领域的一个关键挑战，因为我们仍处于理解细胞如何促进和调节由 LLPS 驱动的功能的早期阶段。在这篇综述中，我们讨论了无序、序列引起的分子相互作用的干扰、翻译后修饰以及各种调节刺激在蛋白质 LLPS 中的作用，特别关注从模拟和理论中获得的见解。我们最后讨论了这些分子驱动力如何改变多组分相分离和选择性。
