This article describes dynamical simulations of the assembly of an icosahedral protein shell around a bicomponent fluid cargo. Our simulations are motivated by bacterial microcompartments, which are protein shells found in bacteria that assemble around a complex of enzymes and other components involved in certain metabolic processes. The simulations demonstrate that the relative interaction strengths among the different cargo species play a key role in determining the amount of each species that is encapsulated, their spatial organization, and the nature of the shell assembly pathways. However, the shell protein–shell protein and shell protein–cargo component interactions that help drive assembly and encapsulation also influence cargo composition within certain parameter regimes. These behaviors are governed by a combination of thermodynamic and kinetic effects. In addition to elucidating how natural microcompartments encapsulate multiple components involved within reaction cascades, these results have implications for efforts in synthetic biology to colocalize alternative sets of molecules within microcompartments to accelerate specific reactions. More broadly, the results suggest that coupling between self-assembly and multicomponent liquid–liquid phase separation may play a role in the organization of the cellular cytoplasm.
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Mechanisms of Scaffold-Mediated Microcompartment Assembly and Size Control
This article describes a theoretical and computational study of the dynamical assembly of a protein shell around a complex consisting of many cargo molecules and long, flexible scaffold molecules. Our study is motivated by bacterial microcompartments, which are proteinaceous organelles that assemble around a condensed droplet of enzymes and reactants. As in many examples of cytoplasmic liquid-liquid phase separation, condensation of the microcompartment interior cargo is driven by flexible scaffold proteins that have weak multivalent interactions with the cargo. Our results predict that the shell size, amount of encapsulated cargo, and assembly pathways depend sensitively on properties of the scaffold, including its length and valency of scaffold-cargo interactions. Moreover, the ability of self-assembling protein shells to change their size to accommodate scaffold molecules of different lengths depends crucially on whether the spontaneous curvature radius of the protein shell is smaller or larger than a characteristic elastic length scale of the shell. Beyond natural microcompartments, these results have important implications for synthetic biology efforts to target alternative molecules for encapsulation by microcompartments or viral shells. More broadly, the results elucidate how cells exploit coupling between self-assembly and liquid-liquid phase separation to organize their interiors.
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- Award ID(s):
- 2011846
- PAR ID:
- 10506776
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- ACS Nano
- Volume:
- 15
- Issue:
- 3
- ISSN:
- 1936-0851
- Page Range / eLocation ID:
- 4197 to 4212
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acsnano.0c05715
