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 The (un)structural biology of biomolecular liquid-liquid phase separation using NMR spectroscopy

2020 ◽  
Vol 295 (8) ◽  
pp. 2375-2384 ◽  
Author(s):  
Anastasia C. Murthy ◽  
Nicolas L. Fawzi
Keyword(s):  
Phase Separation ◽  
Nmr Spectroscopy ◽  
Liquid Phase ◽  
Structural Biology ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Molecular Aspects ◽  
Liquid Liquid Phase Separation

Liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a phenomenon that underlies membraneless compartmentalization of the cell. The underlying molecular interactions that underpin biomolecular LLPS have been of increased interest due to the importance of membraneless organelles in facilitating various biological processes and the disease association of several of the proteins that mediate LLPS. Proteins that are able to undergo LLPS often contain intrinsically disordered regions and remain dynamic in solution. Solution-state NMR spectroscopy has emerged as a leading structural technique to characterize protein LLPS due to the variety and specificity of information that can be obtained about intrinsically disordered sequences. This review discusses practical aspects of studying LLPS by NMR, summarizes recent work on the molecular aspects of LLPS of various protein systems, and discusses future opportunities for characterizing the molecular details of LLPS to modulate phase separation.

scholarly journals Liquid–liquid phase separation in autophagy

2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Nobuo N. Noda ◽  
Zheng Wang ◽  
Hong Zhang
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Protein Aggregation ◽  
Therapeutic Targets ◽  
Liquid Phase Separation ◽  
Autophagosome Formation ◽  
Solid States ◽  
Pathological Conditions ◽  
Liquid Liquid Phase Separation

Liquid–liquid phase separation (LLPS) compartmentalizes and concentrates biomacromolecules into distinct condensates. Liquid-like condensates can transition into gel and solid states, which are essential for fulfilling their different functions. LLPS plays important roles in multiple steps of autophagy, mediating the assembly of autophagosome formation sites, acting as an unconventional modulator of TORC1-mediated autophagy regulation, and triaging protein cargos for degradation. Gel-like, but not solid, protein condensates can trigger formation of surrounding autophagosomal membranes. Stress and pathological conditions cause aberrant phase separation and transition of condensates, which can evade surveillance by the autophagy machinery. Understanding the mechanisms underlying phase separation and transition will provide potential therapeutic targets for protein aggregation diseases.

Dynamic behavior of liquid droplets with enzyme compartmentalization triggered by sequential glycolytic enzyme reactions

2021 ◽  
Author(s):  
Tomoto Ura ◽  
Shunsuke Tomita ◽  
Kentaro Shiraki
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Dynamic Behavior ◽  
Droplet Formation ◽  
Glycolytic Enzyme ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Liquid Droplets ◽  
Enzyme Reactions ◽  
Liquid Liquid Phase Separation

Dynamic droplet formation via liquid-liquid phase separation (LLPS) is believed to be involved in the regulation of various biological processes. Here, a model LLPS system coupled with a sequential glycolytic...

Quantitative Evaluation of Colloidal Stability of Antibody Solutions using PEG-Induced Liquid–Liquid Phase Separation

2014 ◽  
Vol 11 (5) ◽  
pp. 1391-1402 ◽  
Author(s):  
Ying Wang ◽  
Ramil F. Latypov ◽  
Aleksey Lomakin ◽  
Julie A. Meyer ◽  
Bruce A. Kerwin ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Quantitative Evaluation ◽  
Colloidal Stability ◽  
Liquid Phase Separation ◽  
Liquid Liquid Phase Separation

scholarly journals LncRNAs: Architectural Scaffolds or More Potential Roles in Phase Separation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Luo ◽  
Lei Qu ◽  
Feiran Gao ◽  
Jun Lin ◽  
Jian Liu ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Biological Activities ◽  
Disease Diagnosis ◽  
Liquid Phase Separation ◽  
Diagnosis And Treatment ◽  
Biological Processes ◽  
And Function ◽  
Liquid Liquid Phase Separation

Biomolecules specifically aggregate in the cytoplasm and nucleus, driving liquid-liquid phase separation (LLPS) formation and diverse biological processes. Extensive studies have focused on revealing multiple functional membraneless organelles in both the nucleus and cytoplasm. Condensation compositions of LLPS, such as proteins and RNAs affecting the formation of phase separation, have been gradually unveiled. LncRNAs possessing abundant second structures usually promote phase separation formation by providing architectural scaffolds for diverse RNAs and proteins interaction in both the nucleus and cytoplasm. Beyond scaffolds, lncRNAs may possess more diverse functions, such as functioning as enhancer RNAs or buffers. In this review, we summarized current studies on the function of phase separation and its related lncRNAs, mainly in the nucleus. This review will facilitate our understanding of the formation and function of phase separation and the role of lncRNAs in these processes and related biological activities. A deeper understanding of the formation and maintaining of phase separation will be beneficial for disease diagnosis and treatment.

scholarly journals Biomolecular condensates as arbiters of biochemical reactions inside the nucleus

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Guillaume Laflamme ◽  
Karim Mekhail
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Environmental Conditions ◽  
Genome Organization ◽  
Liquid Phase Separation ◽  
Nuclear Space ◽  
Biological Processes ◽  
Biochemical Reactions ◽  
Dynamic Structures ◽  
Liquid Liquid Phase Separation

AbstractLiquid-liquid phase separation (LLPS) has emerged as a central player in the assembly of membraneless compartments termed biomolecular condensates. These compartments are dynamic structures that can condense or dissolve under specific conditions to regulate molecular functions. Such properties allow biomolecular condensates to rapidly respond to changing endogenous or environmental conditions. Here, we review emerging roles for LLPS within the nuclear space, with a specific emphasis on genome organization, expression and repair. Our review highlights the emerging notion that biomolecular condensates regulate the sequential engagement of molecules in multistep biological processes.

scholarly journals Spatiotemporal solidification of α-synuclein inside the liquid droplets

2021 ◽  
Author(s):  
Soumik Ray ◽  
Debdeep Chatterjee ◽  
Semanti Mukherjee ◽  
Komal Patel ◽  
Jaladhar K Mahato ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Protein Aggregation ◽  
Neurodegenerative Disorders ◽  
Physical Mechanism ◽  
Liquid Droplet ◽  
Liquid Droplets ◽  
Single Droplet ◽  
Liquid To Solid Transition ◽  
Liquid Liquid Phase Separation

Liquid-liquid phase separation (LLPS) and subsequent liquid-to-solid transition is implicated in membraneless organelles formation as well as disease associated protein aggregation. However, how liquid-to-solid transition is initiated inside a liquid droplet remains unclear. Here, using studies at single droplet resolution, we show that liquid-to-solid transition of α-synuclein (α-Syn) liquid droplets is associated with significant changes in the local microenvironment as well as secondary structure of the protein, which is prominently observed at the center of the liquid droplets. With the ageing of liquid droplets, the structured core at the center gradually expands and propagates over entire droplets. Further, during droplet fusion, smaller, homogeneous droplets progressively dissolve and supply proteins to the larger, heterogeneous droplets containing solid-like core at their center. The present study will significantly help to under-stand the physical mechanism of LLPS and liquid-to-solid transition in biological compartmentalization as well as in protein aggregation associated with human neurodegenerative disorders.

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