Language
English
Publication Date
6-21-2024
Journal
International Journal of Molecular Sciences
DOI
10.3390/ijms25136825
PMID
38999934
PMCID
PMC11241569
PubMedCentral® Posted Date
6-21-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Biomolecular condensates (BMCs) exhibit physiological and pathological relevance in biological systems. Both liquid and solid condensates play significant roles in the spatiotemporal regulation and organization of macromolecules and their biological activities. Some pathological solid condensates, such as Lewy Bodies and other fibrillar aggregates, have been hypothesized to originate from liquid condensates. With the prevalence of BMCs having functional and dysfunctional roles, it is imperative to understand the mechanism of biomolecular condensate formation and initiation. Using the low-complexity domain (LCD) of heterogenous ribonuclear protein A1 (hnRNPA1) as our model, we monitored initial assembly events using dynamic light scattering (DLS) while modulating pH and salt conditions to perturb macromolecule and condensate properties. We observed the formation of nanometer-sized BMCs (nano-condensates) distinct from protein monomers and micron-sized condensates. We also observed that conditions that solubilize micron-sized protein condensates do not solubilize nano-condensates, indicating that the balance of forces that stabilize nano-condensates and micron-sized condensates are distinct. These findings provide insight into the forces that drive protein phase separation and potential nucleation structures of macromolecular condensation.
Keywords
Dynamic Light Scattering, Humans, Heterogeneous Nuclear Ribonucleoprotein A1, Protein Domains, Biomolecular Condensates, Hydrogen-Ion Concentration, hnRNPA1, biomolecular condensates, nano-condensates, nano-clusters, protein phase separation, neurodegenerative diseases
Published Open-Access
yes
Recommended Citation
Phoebe S Tsoi, Josephine C Ferreon, and Allan Chris M Ferreon, "Initiation of hnRNPA1 Low-Complexity Domain Condensation Monitored by Dynamic Light Scattering" (2024). Faculty, Staff and Students Publications. 6533.
https://digitalcommons.library.tmc.edu/baylor_docs/6533