scholarly journals An in silico LLPS perturbation approach in the design of a novel SARS-CoV-2 spike receptor-binding domain inhibitor

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Divine Mensah Sedzro ◽  
Talifhani Mushiana ◽  
Henrietta Onyinye Uzoeto ◽  
Samuel Cosmas ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Liquid Phase Separation ◽  
Perturbation Approach ◽  
P Bodies ◽  
Important Principle ◽  
Liquid Phases ◽  
Membrane Envelope ◽  
Liquid Liquid Phase Separation ◽  
Chromatin Rearrangement

AbstractThe reversible process where a homogenous fluid de-mixes into two distinctively separate liquid phases is referred to as LLPS (Liquid-liquid phase separation). The resulting liquid is made up of one dilute phase and one condensed phase. An increasing number of studies have shown that the liquid-liquid phase separation is an important principle that underlies intracellular organization in biological systems, forming liquid condensates without a membrane envelope, otherwise known as MLOs (membraneless organelles). Such organelles include the P bodies, nucleolus and stress granules. Moreover, the regulation of many other biological processes such as signal transduction, chromatin rearrangement and RNA metabolism have been linked to the liquid-liquid phase separation.

scholarly journals Interactions between Phase-Separated Liquids and Membrane Surfaces

2021 ◽  
Vol 11 (3) ◽  
pp. 1288
Author(s):  
Samuel Botterbusch ◽  
Tobias Baumgart
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Critical Concentration ◽  
Protein Structures ◽  
Lipid Vesicles ◽  
Liquid Phase Separation ◽  
Membrane Surfaces ◽  
Liquid Phases ◽  
Spherical Droplets ◽  
Liquid Liquid Phase Separation

Liquid-liquid phase separation has recently emerged as an important fundamental organizational phenomenon in biological settings. Most studies of biological phase separation have focused on droplets that “condense” from solution above a critical concentration, forming so-called “membraneless organelles” suspended in solution. However, membranes are ubiquitous throughout cells, and many biomolecular condensates interact with membrane surfaces. Such membrane-associated phase-separated systems range from clusters of integral or peripheral membrane proteins in the plane of the membrane to free, spherical droplets wetting membrane surfaces to droplets containing small lipid vesicles. In this review, we consider phase-separated liquids that interact with membrane surfaces and we discuss the consequences of those interactions. The physical properties of distinct liquid phases in contact with bilayers can reshape the membrane, and liquid-liquid phase separation can construct membrane-associated protein structures, modulate their function, and organize collections of lipid vesicles dynamically. We summarize the common phenomena that arise in these systems of liquid phases and membranes.

scholarly journals Observations and implications of liquid–liquid phase separation at high relative humidities in secondary organic material produced by α-pinene ozonolysis without inorganic salts

2015 ◽  
Vol 15 (22) ◽  
pp. 33379-33405 ◽  
Author(s):  
L. Renbaum-Wolff ◽  
M. Song ◽  
C. Marcolli ◽  
Y. Zhang ◽  
P. F. Liu ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Organic Material ◽  
Phase State ◽  
Liquid Phase Separation ◽  
Inorganic Salts ◽  
Laboratory Studies ◽  
Rich Phase ◽  
Liquid Phases ◽  
Liquid Liquid Phase Separation

Abstract. Particles consisting of secondary organic material (SOM) are abundant in the atmosphere. To predict the role of these particles in climate, visibility, and atmospheric chemistry, information on particle phase state (i.e. single liquid, two liquids, solid and so forth) is needed. This paper focuses on the phase state of SOM particles free of inorganic salts produced by the ozonolysis of α-pinene. Phase transitions were investigated both in the laboratory and with a thermodynamic model over the range of < 0.5 % to 100 % relative humidity (RH) at 290 K. In the laboratory studies, a single phase was observed from 0 to 95 % RH while two liquid phases were observed above 95 % RH. For increasing RH, the mechanism of liquid–liquid phase separation (LLPS) was spinodal decomposition. The RH range at which two liquid phases were observed did not depend on the direction of RH change. In the modelling studies at low RH values, the SOM took up hardly any water and was a single organic-rich phase. At high RH values, the SOM underwent LLPS to form an organic-rich phase and an aqueous phase, consistent with the laboratory studies. The presence of LLPS at high RH-values has consequences for the cloud condensation nuclei (CCN) activity of SOM particles. In the simulated Köhler curves for SOM particles, two local maxima are observed. Depending on the composition of the SOM, the first or second maximum can determine the critical supersaturation for activation. The presence of LLPS at high RH-values can explain inconsistencies between measured CCN properties of SOM particles and hygroscopic growth measured below water saturation.

scholarly journals dSCOPE: a software to detect sequences critical for liquid-liquid phase separation

2021 ◽  
Author(s):  
Shihua Li ◽  
Kai Yu ◽  
Qingfeng Zhang ◽  
Zekun Liu ◽  
Jia Liu ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Large Scale ◽  
Liquid Phase Separation ◽  
Post Translational Modifications ◽  
P Bodies ◽  
Large Scale Analysis ◽  
Cancer Mutations ◽  
And Function ◽  
Liquid Liquid Phase Separation

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.

scholarly journals Liquid–liquid phase separation in secondary organic aerosol particles produced from <i>α</i>-pinene ozonolysis and <i>α</i>-pinene photooxidation with/without ammonia

2019 ◽  
Vol 19 (14) ◽  
pp. 9321-9331 ◽  
Author(s):  
Suhan Ham ◽  
Zaeem Bin Babar ◽  
Jae Bong Lee ◽  
Ho-Jin Lim ◽  
Mijung Song
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Secondary Organic Aerosol ◽  
Cloud Condensation Nuclei ◽  
Aerosol Particles ◽  
Organic Aerosol ◽  
Liquid Phase Separation ◽  
Liquid Phases ◽  
Different Types ◽  
Liquid Liquid Phase Separation

Abstract. Recently, liquid–liquid phase separation (LLPS) of secondary organic aerosol (SOA) particles free of inorganic salts has been intensively studied due to the importance of cloud condensation nuclei (CCN) properties. In this study, we investigated LLPS in four different types of SOA particles generated from α-pinene ozonolysis and α-pinene photooxidation in the absence and presence of ammonia (NH3). LLPS was observed in SOA particles produced from α-pinene ozonolysis at ∼95.8 % relative humidity (RH) and α-pinene ozonolysis with NH3 at ∼95.4 % RH. However, LLPS was not observed in SOA particles produced from α-pinene photooxidation and α-pinene photooxidation with NH3. Based on datasets of the average oxygen to carbon elemental ratio (O:C) for different types of SOA particles from this study and from previous studies, there appears to be a relationship between the occurrence of LLPS and the O:C of the SOA particles. When LLPS was observed, the two liquid phases were present up to ∼100 % RH. This result can help more accurately predict the CCN properties of organic aerosol particles.

scholarly journals Liquid-Liquid Phase Separation of Tau Driven by Hydrophobic Interaction Facilitates Fibrillization of Tau

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

scholarly journals Amyloid Aggregation under the Lens of Liquid–Liquid Phase Separation

2020 ◽  
pp. 368-378
Author(s):  
Yanting Xing ◽  
Aparna Nandakumar ◽  
Aleksandr Kakinen ◽  
Yunxiang Sun ◽  
Thomas P. Davis ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Liquid Phase Separation ◽  
Amyloid Aggregation ◽  
Liquid Liquid Phase Separation

scholarly journals Observation of liquid-liquid phase separation of ataxin-3 and quantitative evaluation of its concentration in a single droplet using Raman microscopy

2021 ◽  
Author(s):  
Kazuki Murakami ◽  
Shinji Kajimoto ◽  
Daiki Shibata ◽  
Kunisato Kuroi ◽  
Fumihiko Fujii ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Quantitative Evaluation ◽  
Raman Microscopy ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Single Droplet ◽  
Liquid Liquid Phase Separation

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...

scholarly journals Targeting NSD2-mediated SRC-3 liquid–liquid phase separation sensitizes bortezomib treatment in multiple myeloma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Liu ◽  
Ying Xie ◽  
Jing Guo ◽  
Xin Li ◽  
Jingjing Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Phase Separation ◽  
Liquid Phase ◽  
Liquid Phase Separation ◽  
Acquired Drug Resistance ◽  
Bortezomib Treatment ◽  
Liquid Liquid Phase Separation

AbstractDevelopment of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid–liquid phase separation to supranormally modify histone H3 lysine 36 dimethylation (H3K36me2) modifications on promoters of anti-apoptotic genes. Targeting SRC-3 or interference of its interactions with NSD2 using a newly developed inhibitor, SI-2, sensitizes BTZ treatment and overcomes drug resistance both in vitro and in vivo. Taken together, our findings elucidate a previously unrecognized orchestration of SRC-3 and NSD2 in acquired drug resistance of MM and suggest that SI-2 may be efficacious for overcoming drug resistance in MM patients.

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