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Rabies Virus Phosphoprotein Exhibits Thermoresponsive Phase Separation with a Lower Critical Solution Temperature.
J Mol Biol
January 2025
Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 38000, Grenoble, France. Electronic address:
Rabies virus (RABV) generates membrane-less liquid organelles (Negri bodies) in the cytoplasm of its host cell, where genome transcription and replication and nucleocapsid assembly take place, but the mechanisms of their assembly and maturation remain to be explained. An essential component of the viral RNA synthesizing machine, the phosphoprotein (P), acts as a scaffold protein for the assembly of these condensates. This intrinsically disordered protein forms star-shaped dimers with N-terminal negatively charged flexible arms and C-terminal globular domains exhibiting a large dipole moment.
View Article and Find Full Text PDFHow Salt and Temperature Drive Reentrant Condensation of Aβ40.
Biochemistry
November 2024
Tata Institute of Fundamental Research Hyderabad 36/P Gopanapally village, Hyderabad, Telangana India 500046.
Within the framework of liquid-liquid phase separation (LLPS), biomolecular condensation orchestrates vital cellular processes, and its dysregulation is implicated in severe pathological conditions. Recent studies highlight the role of intrinsically disordered proteins (IDPs) in LLPS, yet the influence of microenvironmental factors has remained a puzzling factor. Here, via computational simulation of the impact of solution conditions on LLPS behavior of neurologically pathogenic IDP Aβ40, we chanced upon a salt-driven reentrant condensation phenomenon, wherein Aβ40 aggregation increases with low salt concentrations (25-50 mM), followed by a decline with further salt increments.
View Article and Find Full Text PDFCellular Prion Protein Conformational Shift after Liquid-Liquid Phase Separation Regulated by a Polymeric Antagonist and Mutations.
J Am Chem Soc
October 2024
Departments of Neuroscience and Neurology, Yale School of Medicine, 100 College Street, New Haven, Connecticut 06510, United States.
Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins has been associated with neurodegenerative diseases, although direct mechanisms are poorly defined. Here, we report on a maturation process for the cellular prion protein (PrP) that involves a conformational change after LLPS and is regulated by mutations and poly(4-styrenesulfonic acid--maleic acid) (PSCMA), a molecule that has been reported to rescue Alzheimer's disease-related cognitive deficits by antagonizing the interaction between PrP and amyloid-β oligomers (Aβo). We show that PSCMA can induce reentrant LLPS of PrP and lower the saturation concentration () of PrP by 100-fold.
View Article and Find Full Text PDFRare Variant in Associated With Familial Supraventricular Tachycardia and Wolff-Parkinson-White Syndrome.
Circ Genom Precis Med
August 2024
Cardiovascular Research Institute (A.S.P., C.Y.M., Y.A.-S., M.M.H., S.K.L., X.H.T.W.).
Article Synopsis
- Accessory pathways can cause supraventricular tachycardia (SVT) and are linked to serious heart issues, like sudden cardiac death in people with Wolff-Parkinson-White syndrome.
- A study investigated genetic variants in a family with SVT and this syndrome using whole exome sequencing and created a mouse model to test findings.
- A specific genetic variant was found to be associated with SVT symptoms and was linked to unusual heart conduction and structural issues in mice, highlighting its potential role in familial heart conditions.
Observation of reentrant metal-insulator transition in a random-dimer disordered SSH lattice.
Npj Nanophoton
June 2024
Department of Applied Physics, KTH Royal Institute of Technology, Albanova University Centre, Roslagstullsbacken 21, 106 91 Stockholm, Sweden.
The interrelationship between localization, quantum transport, and disorder has remained a fascinating focus in scientific research. Traditionally, it has been widely accepted in the physics community that in one-dimensional systems, as disorder increases, localization intensifies, triggering a metal-insulator transition. However, a recent theoretical investigation [Phys.
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