液-液相分离作为原纤维形成的触发因素。
Liquid-liquid phase separation as triggering factor of fibril formation.
发表日期:2024
作者:
Fereshteh Ramezani Khorsand, Vladimir N Uversky
来源:
Alzheimers & Dementia
摘要:
液-液相分离(LLPS)是指均匀溶液自发转变为两个或多个不混溶相的现象。通过短暂的弱多价大分子相互作用,均匀溶液可以自发地分离成两相:一相富含生物分子,另一相缺乏生物分子。相分离被认为是细胞内无膜细胞器(MLO)和生物分子凝聚体形成的物理化学基础。此外,许多生物过程都依赖于LLPS,例如转录、免疫反应、染色质结构、DNA损伤反应、应激颗粒形成、病毒感染等。相分离的异常可能导致癌症、神经退行性疾病和代谢紊乱等疾病。 LLPS 受多种因素调节,例如进行 LLPS 的分子浓度、盐浓度、pH、温度、翻译后修饰和分子伴侣。最近对生物分子 LLPS 的研究进展迅速,并导致了包含与生物分子分离分析各个方面有关的信息的数据库的开发。然而,仍需要更全面的研究来充分理解 LLPS 的具体分子机制和生物效应。版权所有 © 2024。由 Elsevier Inc. 出版。
Liquid-liquid phase separation (LLPS) refers to the phenomenon, where a homogeneous solution spontaneously undergoes a transition into two or more immiscible phases. Through transient weak multivalent macromolecular interactions, a homogeneous solution can spontaneously separate into two phases: one rich in biomolecules and the other poor in biomolecules. Phase separation is believed to serve as the physicochemical foundation for the formation of membrane-less organelles (MLOs) and bio-molecular condensates within cells. Moreover, numerous biological processes depend on LLPS, such as transcription, immunological response, chromatin architecture, DNA damage response, stress granule formation, viral infection, etc. Abnormalities in phase separation can lead to diseases, such as cancer, neurodegeneration, and metabolic disorders. LLPS is regulated by various factors, such as concentration of molecules undergoing LLPS, salt concentration, pH, temperature, post-translational modifications, and molecular chaperones. Recent research on LLPS of biomolecules has progressed rapidly and led to the development of databases containing information pertaining to various aspects of the biomolecule separation analysis. However, more comprehensive research is still required to fully comprehend the specific molecular mechanisms and biological effects of LLPS.Copyright © 2024. Published by Elsevier Inc.