Abstract
Over the past decade, myriads of studies have highlighted the central role of protein condensation in subcellular compartmentalization and spatiotemporal organization of biological processes. Conceptually, protein condensation stands at the highest level in protein structure hierarchy, accounting for the assembly of bodies ranging from thousands to billions of molecules and for densities ranging from dense liquids to solid materials. In size, protein condensates range from nanocondensates of hundreds of nanometers (mesoscopic clusters) to phase-separated micron-sized condensates. In this review, we focus on protein nanocondensation, a process that can occur in subsaturated solutions and can nucleate dense liquid phases, crystals, amorphous aggregates, and fibers. We discuss the nanocondensation of proteins in the light of general physical principles and examine the biophysical properties of several outstanding examples of nanocondensation. We conclude that protein nanocondensation cannot be fully explained by the conceptual framework of micron-scale biomolecular condensation. The evolution of nanocondensates through changes in density and order is currently under intense investigation, and this should lead to the development of a general theoretical framework, capable of encompassing the full range of sizes and densities found in protein condensates.
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Abbreviations
- ALS:
-
Amyotrophic lateral sclerosis
- BR:
-
Bodies bacterial ribonucleoprotein bodies
- DLS:
-
Dynamic light scattering
- FTD:
-
Frontotemporal dementia
- IR:
-
Insulin receptor
- IDD:
-
Intrinsically disordered domain
- IGF:
-
Insulin-like growth factor
- MRG:
-
Mitochondrial RNA granule
- N-protein:
-
Nucleocapsid protein
- Pol II:
-
RNA polymerase II
- polyQ:
-
Polyglutamine track
- PRM:
-
Proline-rich motif
- RBP:
-
RNA binding protein
- SVs:
-
Synaptic vesicles
- SLS:
-
Static light scattering
- SG:
-
Secretory granule
- SH3:
-
SRC homology 3
- α-Syn:
-
α-Synuclein
- TEM:
-
Transmission electron microscopy.
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Acknowledgements
We thank Professor Michele Solimena for stimulating discussions on protein condensation in secretory granules.
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This work was supported by grants from Universidad Nacional de Quilmes (PUNQ2022 2272), Consejo Nacional de Investigaciones Científicas y Técnicas (PIP2021 1054), and Agencia Nacional de Promoción Científica y Tecnológica (PICT2016 0584), Argentina.
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Toledo, P.L., Gianotti, A.R., Vazquez, D.S. et al. Protein nanocondensates: the next frontier. Biophys Rev 15, 515–530 (2023). https://doi.org/10.1007/s12551-023-01105-1
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DOI: https://doi.org/10.1007/s12551-023-01105-1