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.
Highlights
While lipid-based organelles primarily fulfill these functions in eukaryotes, self-assembling protein shells take the lead in simpler organisms. Viruses surround their genomes with a protein capsid, while bacteria use large icosahedral shells known as bacterial microcompartments (BMCs) to sequester the enzymes and reactions responsible for particular metabolic pathways (Kerfeld et al, 2010; Axen et al, 2014; Shively et al, 1998; Bobik et al, 1999; Erbilgin et al, 2014; Petit et al, 2013; Price and Badger, 1991; Shively et al, 1973; Shively et al, 1973; Kerfeld and Erbilgin, 2015)
Recent AFM experiments demonstrated that hexamers are the basic assembly unit during the assembly of BMC shell facets (Sutter et al, 2016), and the carboxysome major shell proteins crystallize as pentamers and hexamers (Tanaka et al, 2008)
Our simulations show that assembly can proceed by two classes of pathways: (i) a multi-step process in which the cargo forms a dense globule, followed by adsorption, assembly, and budding of shell proteins, or (ii) single-step assembly, with simultaneous aggregation of cargo molecules and shell assembly
Summary
While lipid-based organelles primarily fulfill these functions in eukaryotes, self-assembling protein shells take the lead in simpler organisms. Viruses surround their genomes with a protein capsid, while bacteria use large icosahedral shells known as bacterial microcompartments (BMCs) to sequester the enzymes and reactions responsible for particular metabolic pathways (Kerfeld et al, 2010; Axen et al, 2014; Shively et al, 1998; Bobik et al, 1999; Erbilgin et al, 2014; Petit et al, 2013; Price and Badger, 1991; Shively et al, 1973; Shively et al, 1973; Kerfeld and Erbilgin, 2015). BMC functions have been linked to bacterial growth, carbon fixation, symbiosis, or pathogenesis (Kerfeld and Erbilgin, 2015).
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