Intrinsic Disorder-Based Emergence in Cellular Biology: Physiological and Pathological Liquid-Liquid Phase Transitions in Cells

被引:60
作者
Darling, April L. [1 ,2 ]
Zaslavsky, Boris Y. [3 ]
Uversky, Vladimir N. [1 ,2 ,4 ]
机构
[1] Univ S Florida, Dept Mol Med, Morsani Coll Med, Tampa, FL 33612 USA
[2] Univ S Florida, Byrd Alzheimers Res Inst, Morsani Coll Med, Tampa, FL 33612 USA
[3] Cleveland Diagnost, 3615 Super Ave,Suite 4407B, Cleveland, OH 44114 USA
[4] Russian Acad Sci, Inst Biol Instrumentat, Pushchino 142290, Moscow Region, Russia
关键词
intrinsically disordered protein; intrinsically disordered protein region; liquid-liquid phase transition; protein-protein interaction; protein-nucleic acid interaction; posttranslational modifications; AMYOTROPHIC-LATERAL-SCLEROSIS; NUCLEAR-PORE COMPLEX; PRION-LIKE DOMAINS; PROTEIN POSTTRANSLATIONAL MODIFICATIONS; MOLECULAR RECOGNITION FEATURES; NATIVELY UNFOLDED PROTEINS; SOLVENT PROPERTIES; UNSTRUCTURED PROTEINS; STRUCTURAL DISORDER; BINDING REGIONS;
D O I
10.3390/polym11060990
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
The visible outcome of liquid-liquid phase transitions (LLPTs) in cells is the formation and disintegration of various proteinaceous membrane-less organelles (PMLOs). Although LLPTs and related PMLOs have been observed in living cells for over 200 years, the physiological functions of these transitions (also known as liquid-liquid phase separation, LLPS) are just starting to be understood. While unveiling the functionality of these transitions is important, they have come into light more recently due to the association of abnormal LLPTs with various pathological conditions. In fact, several maladies, such as various cancers, different neurodegenerative diseases, and cardiovascular diseases, are known to be associated with either aberrant LLPTs or some pathological transformations within the resultant PMLOs. Here, we will highlight both the physiological functions of cellular liquid-liquid phase transitions as well as the pathological consequences produced through both dysregulated biogenesis of PMLOs and the loss of their dynamics. We will also discuss the potential downstream toxic effects of proteins that are involved in pathological formations.
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页数:23
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