无序蛋白质在生物分子凝聚相形成与调控中的作用  

How Intrinsically Disordered Proteins Modulate Biomolecular Condensates

作　　者：王妍妍 陈丽敏 李思扬 来鲁华[1] Yanyan Wang;Limin Chen;Siyang Li;Luhua Lai(College of Chemistry and Molecular Engineering,and Academy for Advanced Interdisciplinary Studies,Peking University,Research Unit of Drug Design Method,Chinese Academy of Medical Sciences(2021RU014),Beijing 100871,China)

机构地区：[1]北京大学化学与分子工程学院,北京大学前沿交叉学科研究院,中国医学科学院药物设计方法研究创新单元(2021RU014),北京100871

出　　处：《化学进展》2022年第7期1610-1618,共9页Progress in Chemistry

基　　金：国家自然科学基金项目(No.21633001);中国医学科学院创新基金(No.2021-I2M-5-014)资助。

摘　　要：生物分子凝聚形成生物体内的多种无膜细胞器,其独特的物理化学性质使其具有多样的生物学功能,包括感知外界环境的变化、调节蛋白在细胞内的浓度、调控信号转导途径以及选择性富集特定蛋白质和RNA等。同时,生物分子凝聚相的错误形成与调控会导致多种人类疾病,如神经退行性疾病、癌症和病毒性疾病等。无序蛋白质在生物分子凝聚相的形成和调控中发挥了重要作用。本文通过总结分析无序蛋白在生物分子凝聚相形成中的作用以及化学小分子对生物分子凝聚相的调控,探讨了通过靶向无序蛋白进行配体设计来获得调控生物分子凝聚相化学探针及药物的可能性,并展望了揭示无序蛋白及化学分子调控生物凝聚相机制应重点关注的问题。Biomolecular condensates form various cellular membraneless organelles and play diverse biological functions as a result of their specific physicochemical properties.For example,biomolecular condensates are able to perceive changes in the external environment,regulate the cellular concentration of proteins,modulate different signaling pathways and selectively partition hub proteins as well as nucleic acids.Abnormal formation and changes of biomolecular condensates are closely related to human diseases,especially neurodegenerative diseases,cancers and viral diseases such as COVID-19.Intrinsically disordered proteins(IDPs)play key roles in the formation and regulation of biomolecular condensates.In this review,we analyze the roles that IDPs and small molecules play in biomolecular condensates formation and regulation,propose the possibility of rationally regulating biomolecular condensates through ligand design targeting IDPs,and discuss the challenges of understanding biomolecular condensate formation and regulation mechanisms and for discovering novel chemical compounds to modulate biomolecular condensates.

关 键 词：无序蛋白质 生物分子凝聚相 驱动力 化学小分子调控 

分 类 号：O61[理学—无机化学] O64[理学—化学]