scholarly journals Liquid–liquid phase separation of tau protein: The crucial role of electrostatic interactions

2019 ◽  
Vol 294 (29) ◽  
pp. 11054-11059 ◽  
Author(s):  
Solomiia Boyko ◽  
Xu Qi ◽  
Tien-Hao Chen ◽  
Krystyna Surewicz ◽  
Witold K. Surewicz
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Tau Protein ◽  
Crucial Role ◽  
Electrostatic Interactions ◽  
Liquid Phase Separation ◽  
Liquid Liquid Phase Separation

Quadruplex Folding of DNA Promotes the Condensation of Linker Histones via Liquid-Liquid Phase Separation

2020 ◽  
Author(s):  
Masahiro Mimura ◽  
Shunsuke Tomita ◽  
Yoichi Shinkai ◽  
Kentaro Shiraki ◽  
Ryoji Kurita
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Electrostatic Interactions ◽  
Droplet Formation ◽  
Liquid Phase Separation ◽  
Intrinsically Disordered ◽  
G Quadruplex ◽  
Dna Quadruplex ◽  
Liquid Liquid Phase Separation

<p>Liquid-liquid phase separation (LLPS) of proteins and DNA has recently emerged as a possible mechanism underlying the dynamic organization of chromatin. We herein report the role of DNA quadruplex folding in liquid droplet formation via LLPS induced by interactions between DNA and linker histone H1 (H1), a key regulator of chromatin organization. Fluidity measurements inside the droplets and binding assays using G-quadruplex-selective probes demonstrated that quadruplex DNA structures, such as the G-quadruplex and i-motif, promote droplet formation with H1 and decrease molecular motility within droplets. The dissolution of the droplets in the presence of additives indicated that in addition to electrostatic interactions between the DNA and the intrinsically disordered region of H1, π-π stacking between quadruplex DNAs could potentially drive droplet formation. Given that DNA quadruplex structures are well documented in heterochromatin regions, it is imperative to understand the role of DNA quadruplex folding in the context of intranuclear LLPS.<b></b></p>

scholarly journals Quadruplex Folding of DNA Promotes the Condensation of Linker Histones via Liquid-Liquid Phase Separation

2020 ◽  
Author(s):  
Masahiro Mimura ◽  
Shunsuke Tomita ◽  
Yoichi Shinkai ◽  
Kentaro Shiraki ◽  
Ryoji Kurita
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Electrostatic Interactions ◽  
Droplet Formation ◽  
Liquid Phase Separation ◽  
Intrinsically Disordered ◽  
G Quadruplex ◽  
Dna Quadruplex ◽  
Liquid Liquid Phase Separation

<p>Liquid-liquid phase separation (LLPS) of proteins and DNA has recently emerged as a possible mechanism underlying the dynamic organization of chromatin. We herein report the role of DNA quadruplex folding in liquid droplet formation via LLPS induced by interactions between DNA and linker histone H1 (H1), a key regulator of chromatin organization. Fluidity measurements inside the droplets and binding assays using G-quadruplex-selective probes demonstrated that quadruplex DNA structures, such as the G-quadruplex and i-motif, promote droplet formation with H1 and decrease molecular motility within droplets. The dissolution of the droplets in the presence of additives indicated that in addition to electrostatic interactions between the DNA and the intrinsically disordered region of H1, π-π stacking between quadruplex DNAs could potentially drive droplet formation. Given that DNA quadruplex structures are well documented in heterochromatin regions, it is imperative to understand the role of DNA quadruplex folding in the context of intranuclear LLPS.<b></b></p>

Quadruplex Folding of DNA Promotes the Condensation of Linker Histones via Liquid-Liquid Phase Separation

2020 ◽  
Author(s):  
Masahiro Mimura ◽  
Shunsuke Tomita ◽  
Yoichi Shinkai ◽  
Kentaro Shiraki ◽  
Ryoji Kurita
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Electrostatic Interactions ◽  
Droplet Formation ◽  
Liquid Phase Separation ◽  
Intrinsically Disordered ◽  
G Quadruplex ◽  
Dna Quadruplex ◽  
Liquid Liquid Phase Separation

<p>Liquid-liquid phase separation (LLPS) of proteins and DNA has recently emerged as a possible mechanism underlying the dynamic organization of chromatin. We herein report the role of DNA quadruplex folding in liquid droplet formation via LLPS induced by interactions between DNA and linker histone H1 (H1), a key regulator of chromatin organization. Fluidity measurements inside the droplets and binding assays using G-quadruplex-selective probes demonstrated that quadruplex DNA structures, such as the G-quadruplex and i-motif, promote droplet formation with H1 and decrease molecular motility within droplets. The dissolution of the droplets in the presence of additives indicated that in addition to electrostatic interactions between the DNA and the intrinsically disordered region of H1, π-π stacking between quadruplex DNAs could potentially drive droplet formation. Given that DNA quadruplex structures are well documented in heterochromatin regions, it is imperative to understand the role of DNA quadruplex folding in the context of intranuclear LLPS.<b></b></p>

scholarly journals Role of protein conformation and weak interactions on γ-gliadin liquid-liquid phase separation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Line Sahli ◽  
Denis Renard ◽  
Véronique Solé-Jamault ◽  
Alexandre Giuliani ◽  
Adeline Boire
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Electrostatic Interactions ◽  
Storage Proteins ◽  
Liquid Phase Separation ◽  
Water Mixture ◽  
Terminal Domain ◽  
Liquid Liquid Phase Separation

Abstract Wheat storage proteins, gliadins, were found to form in vitro condensates in 55% ethanol/water mixture by decreasing temperature. The possible role of this liquid-liquid phase separation (LLPS) process on the in vivo gliadins storage is elusive and remains to be explored. Here we use γ-gliadin as a model of wheat proteins to probe gliadins behavior in conditions near physiological conditions. Bioinformatic analyses suggest that γ-gliadin is a hybrid protein with N-terminal domain predicted to be disordered and C-terminal domain predicted to be ordered. Spectroscopic data highlight the disordered nature of γ-gliadin. We developed an in vitro approach consisting to first solubilize γ-gliadin in 55% ethanol (v/v) and to progressively decrease ethanol ratio in favor of increased aqueous solution. Our results show the ability of γ-gliadin to self-assemble into dynamic droplets through LLPS, with saturation concentrations ranging from 25.9 µM ± 0.85 µM (35% ethanol (v/v)) to 3.8 µM ± 0.1 µM (0% ethanol (v/v)). We demonstrate the importance of the predicted ordered C-terminal domain of γ-gliadin in the LLPS by highlighting the protein condensates transition from a liquid to a solid state under reducing conditions. We demonstrate by increasing ionic strength the role displayed by electrostatic interactions in the phase separation. We also show the importance of hydrogen bonds in this process. Finally, we discuss the importance of gliadins condensates in their accumulation and storage in the wheat seed.

scholarly journals Quadruplex folding promotes the condensation of linker histones and DNAs via liquid-liquid phase separation

2021 ◽  
Author(s):  
Masahiro Mimura ◽  
Shunsuke Tomita ◽  
Yoichi Shinkai ◽  
Takuya Hosokai ◽  
Hiroyuki Kumeta ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Electrostatic Interactions ◽  
Droplet Formation ◽  
Liquid Phase Separation ◽  
Intrinsically Disordered ◽  
G Quadruplex ◽  
Dna Quadruplex ◽  
Liquid Liquid Phase Separation

Liquid-liquid phase separation (LLPS) of proteins and DNA has recently emerged as a possible mechanism underlying the dynamic organization of chromatin. We herein report the role of DNA quadruplex folding in liquid droplet formation via LLPS induced by interactions between DNA and linker histone H1 (H1), a key regulator of chromatin organization. <a>Fluidity measurements inside the droplets, binding assays using G-quadruplex-selective probes, and structural analyses based on circular dichroism demonstrated that quadruplex DNA structures, such as the G-quadruplex and i-motif, promote droplet formation with H1 and decrease molecular motility within droplets. </a><a></a><a></a><a>The dissolution of the droplets in the presence of additives and the LLPS of the DNA structural units indicated that in addition to electrostatic interactions between the DNA and the intrinsically disordered region of H1, π-π stacking between quadruplex DNAs could potentially drive droplet formation, unlike in the electrostatically driven LLPS of duplex DNA and H1. According to phase diagrams of anionic molecules with various conformations, the high LLPS ability associated with quadruplex folding arises from the formation of interfaces consisting of organized planes of guanine bases and the side surfaces with high charge density. </a>Given that DNA quadruplex structures are well documented in heterochromatin regions, it is imperative to understand the role of DNA quadruplex folding in the context of intranuclear LLPS.<br>

scholarly journals Deciphering the Role of π-Interactions in Polyelectrolyte Complexes Using Rationally Designed Peptides

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2074
Author(s):  
Sara Tabandeh ◽  
Cristina Elisabeth Lemus ◽  
Lorraine Leon
Keyword(s):  
Hydrogen Bonding ◽  
Phase Separation ◽  
Liquid Phase ◽  
Charge Density ◽  
Secondary Structures ◽  
Liquid Phase Separation ◽  
Polyelectrolyte Complexes ◽  
Π Interactions ◽  
Liquid Liquid Phase Separation

Electrostatic interactions, and specifically π-interactions play a significant role in the liquid-liquid phase separation of proteins and formation of membraneless organelles/or biological condensates. Sequence patterning of peptides allows creating protein-like structures and controlling the chemistry and interactions of the mimetic molecules. A library of oppositely charged polypeptides was designed and synthesized to investigate the role of π-interactions on phase separation and secondary structures of polyelectrolyte complexes. Phenylalanine was chosen as the π-containing residue and was used together with lysine or glutamic acid in the design of positively or negatively charged sequences. The effect of charge density and also the substitution of fluorine on the phenylalanine ring, known to disrupt π-interactions, were investigated. Characterization analysis using MALDI-TOF mass spectroscopy, H NMR, and circular dichroism (CD) confirmed the molecular structure and chiral pattern of peptide sequences. Despite an alternating sequence of chirality previously shown to promote liquid-liquid phase separation, complexes appeared as solid precipitates, suggesting strong interactions between the sequence pairs. The secondary structures of sequence pairs showed the formation of hydrogen-bonded structures with a β-sheet signal in FTIR spectroscopy. The presence of fluorine decreased hydrogen bonding due to its inhibitory effect on π-interactions. π-interactions resulted in enhanced stability of complexes against salt, and higher critical salt concentrations for complexes with more π-containing amino acids. Furthermore, UV-vis spectroscopy showed that sequences containing π-interactions and increased charge density encapsulated a small charged molecule with π-bonds with high efficiency. These findings highlight the interplay between ionic, hydrophobic, hydrogen bonding, and π-interactions in polyelectrolyte complex formation and enhance our understanding of phase separation phenomena in protein-like structures.

scholarly journals Liquid–liquid phase separation in human health and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Bin Wang ◽  
Lei Zhang ◽  
Tong Dai ◽  
Ziran Qin ◽  
Huasong Lu ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Human Health ◽  
Essential Role ◽  
Current Knowledge ◽  
Vital Role ◽  
Liquid Phase Separation ◽  
Eukaryotic Cells ◽  
Liquid Liquid Phase Separation

AbstractEmerging evidence suggests that liquid–liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions. We further describe the role of LLPS in the development of human diseases. Additionally, we review the recently developed methods for studying LLPS. Although LLPS research is in its infancy—but is fast-growing—it is clear that LLPS plays an essential role in the development of pathophysiological conditions. This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.

scholarly journals Taurine suppresses liquid-liquid phase separation of lysozyme protein

2021 ◽  
Author(s):  
Kanae Tsubotani ◽  
Sayuri Maeyama ◽  
Shigeru Murakami ◽  
Stephen W Schaffer ◽  
Takashi Ito
Keyword(s):  
Phase Separation ◽  
Polyethylene Glycol ◽  
Critical Temperature ◽  
Liquid Phase ◽  
Liquid Phase Separation ◽  
Compatible Osmolyte ◽  
Hen Egg ◽  
Liquid Liquid Phase Separation ◽  
In Cells

AbstractTaurine is a compatible osmolyte that infers stability to proteins. Recent studies have revealed that liquid-liquid phase separation (LLPS) of proteins underlie the formation of membraneless organelles in cells. In the present study, we evaluated the role of taurine on LLPS of hen egg lysozyme. We demonstrated that taurine decreases the turbidity of the polyethylene glycol-induced crowding solution of lysozyme. We also demonstrated that taurine attenuates LLPS-dependent cloudiness of lysozyme solution with 0.5 or 1M NaCl at a critical temperature. Moreover, we observed that taurine inhibits LLPS formation of a heteroprotein mix solution of lysozyme and ovalbumin. These data indicate that taurine can modulate the formation of LLPS of proteins.

scholarly journals Bi-directional protein-protein interactions control liquid-liquid phase separation of PSD-95 and its interaction partners

2021 ◽  
Author(s):  
Nikolaj Riis Christensen ◽  
Christian Parsbæk Pedersen ◽  
Vita Sereikaite ◽  
Jannik Nedergaard Pedersen ◽  
Maria Vistrup-Parry ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Protein Interactions ◽  
Postsynaptic Density ◽  
Specific Protein ◽  
Liquid Phase Separation ◽  
Protein Protein Interactions ◽  
New Perspective ◽  
Liquid Liquid Phase Separation

SUMMARYThe organization of the postsynaptic density (PSD), a protein-dense semi-membraneless organelle, is mediated by numerous specific protein-protein interactions (PPIs) which constitute a functional post-synapse. Postsynaptic density protein 95 (PSD-95) interacts with a manifold of proteins, including the C-terminal of transmembrane AMPA receptor (AMAPR) regulatory proteins (TARPs). Here, we uncover the minimal essential peptide responsible for the stargazin (TARP-γ2) mediated liquid-liquid phase separation (LLPS) formation of PSD-95 and other key protein constituents of the PSD. Furthermore, we find that pharmacological inhibitors of PSD-95 can facilitate formation of LLPS. We found that in some cases LLPS formation is dependent on multivalent interactions while in other cases short peptides carrying a high charge are sufficient to promote LLPS in complex systems. This study offers a new perspective on PSD-95 interactions and their role in LLPS formation, while also considering the role of affinity over multivalency in LLPS systems.

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