Regulation of Liquid-Liquid Phase Separation with Focus on Post-Translational Modifications

2021 ◽  
Author(s):  
Yun-Yi Luo ◽  
Jun-Jun Wu ◽  
Yan-Mei Li

Liquid-liquid phase separation (LLPS), a type of phase transition that is important in organisms, is an unique means of forming biomolecular condensates. LLPS plays a significant role in transcription, genome...

2020 ◽  
Author(s):  
Hiroya Tange ◽  
Daisuke Ishibashi ◽  
Takehiro Nakagaki ◽  
Yuzuru Taguchi ◽  
Yuji O. Kamatari ◽  
...  

AbstractPrion diseases are characterized by accumulation of amyloid fibrils. The causative agent is an infectious amyloid that is comprised solely of misfolded prion protein (PrPSc). Prions can convert PrPC to proteinase-resistant PrP (PrP-res) in vitro; however, the intermediate steps involved in the spontaneous conversion remain unknown. We investigated whether recombinant prion protein (rPrP) can directly convert into PrP-res via liquid-liquid phase separation in the absence of PrPSc. We found that rPrP underwent liquid-liquid phase separation at the interface of the aqueous two-phase system (ATPS) of polyethylene glycol (PEG) and dextran, whereas single-phase conditions were not inducible. Fluorescence recovery assay after photobleaching revealed that the liquid-solid phase transition occurred within a short time. The aged rPrP-gel acquired proteinase-resistant amyloid accompanied by β-sheet conversion, as confirmed by western blotting, Fourier transform infrared spectroscopy, and Congo red staining. The reactions required both the N-terminal region of rPrP (amino acids 23-89) and kosmotropic salts, suggesting that the kosmotropic anions may interact with the N-terminal region of rPrP to promote liquid-liquid phase separation. Thus, structural conversion via liquid–liquid phase separation and liquid–solid phase transition are intermediate steps in the conversion of prions.


Soft Matter ◽  
2022 ◽  
Author(s):  
Paul Pullara ◽  
Ibraheem Alshareedah ◽  
Priya Banerjee

Liquid-liquid phase separation (LLPS) of multivalent biopolymers is a ubiquitous process in biological systems and is of importance in bio-mimetic soft matter design. The phase behavior of biomolecules, such as...


2021 ◽  
Author(s):  
Shihua Li ◽  
Kai Yu ◽  
Qingfeng Zhang ◽  
Zekun Liu ◽  
Jia Liu ◽  
...  

ABSTRACTMembrane based cells are the fundamental structure and function units of organisms, while evidences were increasing that liquid-liquid phase separation (LLPS) is associated with the formation of membraneless organelles, such as P-bodies, nucleoli and stress granules. Many studies have been undertaken to explore the functions of protein phase separation, but these studies lacked an effective tool to identify the sequence segments that critical for LLPS (SCOPEs). In this study, we presented a novel software called dSCOPE (http://dscope.omicsbio.info) to predict the SCOPEs. To develop the predictor, we curated experimentally identified sequence segments that can drive LLPS from published literature. Then sliding sequence window based physiological, biochemical, structural and coding features were integrated by random forest algorithm to perform prediction. Through rigorous evaluation, dSCOPE was demonstrated to achieve satisfactory performance. Furthermore, large-scale analysis of human proteome based on dSCOPE showed that the predicted SCOPEs enriched various protein post-translational modifications and cancer mutations, and the proteins which contain predicted SCOPEs enriched critical cellular signaling pathways. Taken together, dSCOPE precisely predicted the protein sequence segments critical for LLPS, with various helpful information visualized in the webserver to facilitate LLPS related research.


2019 ◽  
Vol 48 (D1) ◽  
pp. D288-D295 ◽  
Author(s):  
Wanshan Ning ◽  
Yaping Guo ◽  
Shaofeng Lin ◽  
Bin Mei ◽  
Yu Wu ◽  
...  

Abstract Here, we presented an integrative database named DrLLPS (http://llps.biocuckoo.cn/) for proteins involved in liquid–liquid phase separation (LLPS), which is a ubiquitous and crucial mechanism for spatiotemporal organization of various biochemical reactions, by creating membraneless organelles (MLOs) in eukaryotic cells. From the literature, we manually collected 150 scaffold proteins that are drivers of LLPS, 987 regulators that contribute in modulating LLPS, and 8148 potential client proteins that might be dispensable for the formation of MLOs, which were then categorized into 40 biomolecular condensates. We searched potential orthologs of these known proteins, and in total DrLLPS contained 437 887 known and potential LLPS-associated proteins in 164 eukaryotes. Furthermore, we carefully annotated LLPS-associated proteins in eight model organisms, by using the knowledge integrated from 110 widely used resources that covered 16 aspects, including protein disordered regions, domain annotations, post-translational modifications (PTMs), genetic variations, cancer mutations, molecular interactions, disease-associated information, drug-target relations, physicochemical property, protein functional annotations, protein expressions/proteomics, protein 3D structures, subcellular localizations, mRNA expressions, DNA & RNA elements, and DNA methylations. We anticipate DrLLPS can serve as a helpful resource for further analysis of LLPS.


2021 ◽  
Vol 433 (2) ◽  
pp. 166731
Author(s):  
Yanxian Lin ◽  
Yann Fichou ◽  
Andrew P. Longhini ◽  
Luana C. Llanes ◽  
Pengyi Yin ◽  
...  

Author(s):  
Yanting Xing ◽  
Aparna Nandakumar ◽  
Aleksandr Kakinen ◽  
Yunxiang Sun ◽  
Thomas P. Davis ◽  
...  

2021 ◽  
Author(s):  
Kazuki Murakami ◽  
Shinji Kajimoto ◽  
Daiki Shibata ◽  
Kunisato Kuroi ◽  
Fumihiko Fujii ◽  
...  

Liquid–liquid phase separation (LLPS) plays an important role in a variety of biological processes and is also associated with protein aggregation in neurodegenerative diseases. Quantification of LLPS is necessary to...


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