Holehouse Alex S, Alberti Simon
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; Center for Biomolecular Condensates (CBC), Washington University in St. Louis, St. Louis, MO, USA.
Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
Mol Cell. 2025 Jan 16;85(2):290-308. doi: 10.1016/j.molcel.2024.12.021.
Cells use membraneless compartments to organize their interiors, and recent research has begun to uncover the molecular principles underlying their assembly. Here, we explore how site-specific and chemically specific interactions shape the properties and functions of condensates. Site-specific recruitment involves precise interactions at specific sites driven by partially or fully structured interfaces. In contrast, chemically specific recruitment is driven by complementary chemical interactions without the requirement for a persistent bound-state structure. We propose that site-specific and chemically specific interactions work together to determine the composition of condensates, facilitate biochemical reactions, and regulate enzymatic activities linked to metabolism, signaling, and gene expression. Characterizing the composition of condensates requires novel experimental and computational tools to identify and manipulate the molecular determinants guiding condensate recruitment. Advancing this research will deepen our understanding of how condensates regulate cellular functions, providing valuable insights into cellular physiology and organization.
细胞利用无膜区室来组织其内部结构,最近的研究已开始揭示其组装背后的分子原理。在这里,我们探讨位点特异性和化学特异性相互作用如何塑造凝聚物的性质和功能。位点特异性招募涉及由部分或完全结构化界面驱动的在特定位点的精确相互作用。相比之下,化学特异性招募是由互补的化学相互作用驱动的,而不需要持久的结合态结构。我们提出,位点特异性和化学特异性相互作用共同作用,以确定凝聚物的组成,促进生化反应,并调节与代谢、信号传导和基因表达相关的酶活性。表征凝聚物的组成需要新颖的实验和计算工具,以识别和操纵指导凝聚物招募的分子决定因素。推进这项研究将加深我们对凝聚物如何调节细胞功能的理解,为细胞生理学和组织提供有价值的见解。