Abstract
Bacterial microcompartments are large, roughly icosahedral shells that assemble around enzymes and reactants involved in certain metabolic pathways in bacteria. Motivated by microcompartment assembly, we use coarse-grained computational and theoretical modeling to study the factors that control the size and morphology of a protein shell assembling around hundreds to thousands of molecules. We perform dynamical simulations of shell assembly in the presence and absence of cargo over a range of interaction strengths, subunit and cargo stoichiometries, and the shell spontaneous curvature. Depending on these parameters, we find that the presence of a cargo can either increase or decrease the size of a shell relative to its intrinsic spontaneous curvature, as seen in recent experiments. These features are controlled by a balance of kinetic and thermodynamic effects, and the shell size is assembly pathway dependent. We discuss implications of these results for synthetic biology efforts to target new enzymes to microcompartment interiors.
Highlights
While it has long been recognized that membrane-bound organelles organize the cytoplasm of eukaryotes, it is evident that protein-based compartments play a similar role in many organisms
To simulate the dynamics of microcompartment assembly, we build on the model developed by Perlmutter et al [42], which allowed only a single energy minimum shell geometry, The role of the encapsulated cargo in microcompartment assembly corresponding to a T = 3 icosahedral shell containing 12 pentamers and 20 hexamers
Based on AFM experiments showing that bacterial microcompartments (BMCs) shell facets assemble from pre-formed hexamers [60], and the fact that carboxysome major shell proteins crystallize as pentamers and hexamers [30], our model considers pentamers and hexamers as the basic assembly units
Summary
While it has long been recognized that membrane-bound organelles organize the cytoplasm of eukaryotes, it is evident that protein-based compartments play a similar role in many organisms. Bacterial microcompartments (BMCs) are icosahedral proteinaceous organelles that assemble around enzymes and reactants to compartmentalize certain metabolic pathways [1,2,3,4,5,6,7,8,9,10]. Understanding the factors that control the assembly of BMCs and other protein-based organelles is a fundamental aspect of cell biology. From a synthetic biology perspective, understanding factors that control packaging of the interior cargo will allow reengineering BMCs as nanocompartments that encapsulate a programmable set of enzymes, to introduce new or improved metabolic pathways into bacteria or other organisms Understanding how the properties of a cargo affect the assembly of its encapsulating container is important for drug delivery and nanomaterials applications
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