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Assemblages: functional units formed by cellular phase separation.

Toretsky JA, Wright PE - J. Cell Biol. (2014)

Bottom Line: The partitioning of intracellular space beyond membrane-bound organelles can be achieved with collections of proteins that are multivalent or contain low-complexity, intrinsically disordered regions.These proteins can undergo a physical phase change to form functional granules or other entities within the cytoplasm or nucleoplasm that collectively we term "assemblage." Intrinsically disordered proteins (IDPs) play an important role in forming a subset of cellular assemblages by promoting phase separation.Recent work points to an involvement of assemblages in disease states, indicating that intrinsic disorder and phase transitions should be considered in the development of therapeutics.

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Affiliation: Department of Oncology, Georgetown University, Washington, DC 20057 jat42@georgetown.edu.

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Assemblage formation leads to emergent properties of protein and RNA binding. This series of panels (A–D) demonstrates that an increase in the local concentration of protein (yellow ribbons) in regions of a cell can result in a phase transition (yellow haze) to form an assemblage once a critical concentration has been reached. A phase separated assemblage can be formed through weak homotypic or heterotypic interactions and allows exchange of constituent molecules with the surrounding solution. This phase-separated material allows for the capture and interaction of other protein or RNA species (cyan molecule). (D) The final assemblage formation shows the sequestration of two RNA molecules.
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fig1: Assemblage formation leads to emergent properties of protein and RNA binding. This series of panels (A–D) demonstrates that an increase in the local concentration of protein (yellow ribbons) in regions of a cell can result in a phase transition (yellow haze) to form an assemblage once a critical concentration has been reached. A phase separated assemblage can be formed through weak homotypic or heterotypic interactions and allows exchange of constituent molecules with the surrounding solution. This phase-separated material allows for the capture and interaction of other protein or RNA species (cyan molecule). (D) The final assemblage formation shows the sequestration of two RNA molecules.

Mentions: Protein–protein or protein–RNA interactions in an assemblage are multivalent and dynamic, and can be mediated by IDRs of low-complexity or multivalent folded protein domains (Fig. 1). IDPs play an important role in assemblages based upon their ability to dynamically associate either homotypically or heterotypically. The emergent properties that occur in response to a phase transition include the ability to bind RNA or protein in novel interactions (Fig. 1). Polymer physics, including the theories of P. Flory and W. Stockmayer, can contribute to the numerical modeling of assemblages (for a review and detailed discussion of analytical models, see Falkenberg et al., 2013). To discuss the phenomenon of assemblage, an understanding of the biochemical and biophysical underpinnings of phase transitions leading to separation is necessary.


Assemblages: functional units formed by cellular phase separation.

Toretsky JA, Wright PE - J. Cell Biol. (2014)

Assemblage formation leads to emergent properties of protein and RNA binding. This series of panels (A–D) demonstrates that an increase in the local concentration of protein (yellow ribbons) in regions of a cell can result in a phase transition (yellow haze) to form an assemblage once a critical concentration has been reached. A phase separated assemblage can be formed through weak homotypic or heterotypic interactions and allows exchange of constituent molecules with the surrounding solution. This phase-separated material allows for the capture and interaction of other protein or RNA species (cyan molecule). (D) The final assemblage formation shows the sequestration of two RNA molecules.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4151146&req=5

fig1: Assemblage formation leads to emergent properties of protein and RNA binding. This series of panels (A–D) demonstrates that an increase in the local concentration of protein (yellow ribbons) in regions of a cell can result in a phase transition (yellow haze) to form an assemblage once a critical concentration has been reached. A phase separated assemblage can be formed through weak homotypic or heterotypic interactions and allows exchange of constituent molecules with the surrounding solution. This phase-separated material allows for the capture and interaction of other protein or RNA species (cyan molecule). (D) The final assemblage formation shows the sequestration of two RNA molecules.
Mentions: Protein–protein or protein–RNA interactions in an assemblage are multivalent and dynamic, and can be mediated by IDRs of low-complexity or multivalent folded protein domains (Fig. 1). IDPs play an important role in assemblages based upon their ability to dynamically associate either homotypically or heterotypically. The emergent properties that occur in response to a phase transition include the ability to bind RNA or protein in novel interactions (Fig. 1). Polymer physics, including the theories of P. Flory and W. Stockmayer, can contribute to the numerical modeling of assemblages (for a review and detailed discussion of analytical models, see Falkenberg et al., 2013). To discuss the phenomenon of assemblage, an understanding of the biochemical and biophysical underpinnings of phase transitions leading to separation is necessary.

Bottom Line: The partitioning of intracellular space beyond membrane-bound organelles can be achieved with collections of proteins that are multivalent or contain low-complexity, intrinsically disordered regions.These proteins can undergo a physical phase change to form functional granules or other entities within the cytoplasm or nucleoplasm that collectively we term "assemblage." Intrinsically disordered proteins (IDPs) play an important role in forming a subset of cellular assemblages by promoting phase separation.Recent work points to an involvement of assemblages in disease states, indicating that intrinsic disorder and phase transitions should be considered in the development of therapeutics.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Georgetown University, Washington, DC 20057 jat42@georgetown.edu.

Show MeSH
Related in: MedlinePlus