title: Many-molecule encapsulation by an icosahedral shell.
abstract: We computationally study how an icosahedral shell assembles around hundreds of molecules. Such a process occurs during the formation of the carboxysome, a bacterial microcompartment that assembles around many copies of the enzymes ribulose 1,5-bisphosphate carboxylase/ oxygenase and carbonic anhydrase to facilitate carbon fixation in cyanobacteria. Our simulations identify two classes of assembly pathways leading to encapsulation of many-molecule cargoes. In one, shell assembly proceeds concomitantly with cargo condensation. In the other, the cargo first forms a dense globule; then, shell proteins assemble around and bud from the condensed cargo complex. Although the model is simplified, the simulations predict intermediates and closure mechanisms not accessible in experiments, and show how assembly can be tuned between these two pathways by modulating protein interactions. In addition to elucidating assembly pathways and critical control parameters for microcompartment assembly, our results may guide the reengineering of viruses as nanoreactors that self-assemble around their reactants.
authors.affiliation: Martin Fisher School of Physics, Brandeis University, Waltham, United States.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Perlmutter
authors.affiliation: Martin Fisher School of Physics, Brandeis University, Waltham, United States.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Mohajerani
authors.affiliation: Martin Fisher School of Physics, Brandeis University, Waltham, United States.
authors.forename: Michael F
authors.identifier: 0000-0002-9211-2434
authors.initials: MF
authors.lastname: Hagan
mesh_terms: D046911:Macromolecular Substances / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D009097:Multienzyme Complexes
keywords: E. coli; bacterial microcompartment; biophysics; carboxysome; computational biology; self-assembly; simulation; structural biology; systems biology; viral capsid; virus