phase separation behavior
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2021 ◽  
Author(s):  
Michael L Nosella ◽  
Maria Tereshchenko ◽  
Iva Pritisanac ◽  
Andrew Chong ◽  
Jeffrey A Toretsky ◽  
...  

Many membraneless organelles are thought to be biomolecular condensates formed by phase separation of proteins and other biopolymers. Post-translational modifications (PTMs) can impact protein phase separation behavior, although for many PTMs this aspect of their function is unknown. O-linked β-D-N-acetylglucosaminylation (O-GlcNAcylation) is an abundant form of intracellular glycosylation whose roles in regulating biomolecular condensate assembly and dynamics have not been delineated. Using an in vitro approach, we found that O-GlcNAcylation reduces the phase separation propensity of the EWS N-terminal low complexity region (LCRN) under different conditions, including in the presence of the arginine- and glycine-rich RNA-binding do- mains (RBD). O-GlcNAcylation enhances fluorescence recovery after photobleaching (FRAP) within EWS LCRN condensates and causes the droplets to exhibit more liquid-like relaxation following fusion. Following extended incubation times, EWS LCRN+RBD condensates exhibit diminished FRAP, indicating a loss of fluidity, while condensates containing the O-GlcNAcylated LCRN do not. In HeLa cells, EWS is less O-GlcNAcylated following OGT knockdown and more prone to aggregation based on a filter retardation assay. Relative to the human proteome, O-GlcNAcylated proteins are enriched with regions that are predicted to phase separate, suggesting a general role of O-GlcNAcylation in regulation of biomolecular condensates.


Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1027
Author(s):  
Chuanai Cao ◽  
Xin Li ◽  
Yongchao Yin ◽  
Baohua Kong ◽  
Fangda Sun ◽  
...  

The objective of this study was to investigate the influence of sodium chloride (NaCl) concentration (0–500 mM) on the physical and oxidative stabilities of filled hydrogel that were stabilized using heat-denatured whey protein concentrate and high methoxy pectin. Our results showed that with an increase in NaCl concentration, the particle sizes, zeta-potentials, and interfacial layer thickness of filled hydrogels significantly increased and the lightness and whiteness gradually decreased (p < 0.05). Moreover, rheological characterization revealed that the apparent viscosity and viscoelastic behavior gradually decreased at higher NaCl concentration, which was mainly ascribed to the influence of NaCl on the electrostatic repulsion between droplets, thereby adversely impacting the physical stability of filled hydrogels. Furthermore, the result of cryo-scanning electron microscopy also verified the abovementioned results. Notably, higher NaCl concentration significantly promoted the oxidation of lipids and proteins (p < 0.05), thereby decreasing the oxidative stabilities of filled hydrogels. Our results indicated that filled hydrogels prepared under different ionic strength conditions can provide the theoretical basis for their future application in emulsion-based foods.


Author(s):  
Xuejiao Jin ◽  
Xiuling Cao ◽  
Shenkui Liu ◽  
Beidong Liu

Stress granules (SGs) are highly dynamic cytoplasmic foci formed in response to stress. The formation of SGs is reported to be regulated by diverse post-translational protein modifications (PTMs). Among them, ADP-ribosylation is of emerging interest due to its recently identified roles in SG organization. In this review, we summarized the latest advances on the roles of poly(ADP-ribose) (PAR) in the regulation of SG formation and dynamics, including its function in modulating nucleocytoplasmic trafficking and SG recruitment of SG components, as well as its effects on protein phase separation behavior. Moreover, the functional role of PAR chain diversity on dynamic of SG composition is also introduced. Potential future developments on investigating global ADP-ribosylation networks, individual roles of different PARPs, and interactions between ADP-ribosylation and other PTMs in SGs are also discussed.


2021 ◽  
Author(s):  
Tongyin Zheng ◽  
Carlos A. Castañeda

AbstractShuttle protein UBQLN2 functions in protein quality control (PQC) by binding to proteasomal receptors and ubiquitinated substrates via its N-terminal ubiquitin-like (UBL) and C-terminal ubiquitin-associated (UBA) domains, respectively. Between these two folded domains are intrinsically disordered STI1-I and STI1-II regions, connected by disordered linkers. The STI1 regions bind other components, such as HSP70, that are important to the PQC functions of UBQLN2. We recently determined that the STI1-II region enables UBQLN2 to undergo liquid-liquid phase separation (LLPS) to form liquid dropletsin vitroand biomolecular condensates in cells. However, how the interplay between the folded (UBL/UBA) domains and the intrinsically-disordered regions mediates phase separation is largely unknown. Using engineered domain deletion constructs, we found that removing the UBA domain inhibits UBQLN2 LLPS while removing the UBL domain enhances LLPS, suggesting that UBA and UBL domains contribute asymmetrically in modulating UBQLN2 LLPS. To explain these differential effects, we interrogated the interactions that involve the UBA and UBL domains across the entire UBQLN2 molecule using NMR spectroscopy. To our surprise, aside from well-studied canonical UBL:UBA interactions, there also exist moderate and weak interactions between the UBL and STI1-I/STI1-II domains, and between the UBA domain and the linker connecting the two STI1 regions, respectively. Our findings are essential for the understanding of both the molecular driving forces of UBQLN2 LLPS and the effects of ligand binding to UBL, UBA, or STI1 domains on the phase behavior and physiological functions of UBQLN2.Impact of Work StatementZheng and Castañeda show that interplay between the folded domains and intrinsically disordered regions regulates liquid-liquid phase separation behavior of UBQLN2, a protein quality control (PQC) shuttle protein. Despite their similar size, the folded UBL and UBA domains inhibit and promote phase separation, respectively, due to their previously uncharacterized, asymmetric interactions with the middle intrinsically-disordered region. These results strongly suggest that PQC components, including proteasomal receptors, are likely to modulate UBQLN2 phase separation behavior in cells.


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