Bioinformatic Identification and Structural Characterization of a New Carboxysome Shell Protein

Abstract

Bacterial Microcompartments (BMCs) are organelles composed of a polyhedral protein shell that encapsulates metabolically related enzymes. The best characterized BMC, the carboxysome, which functions to enhance CO2 fixation by D-ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO), is found in all cyanobacteria. It is an essential part of the cyanobacterial CO2 concentrating mechanism. The shell of BMCs is composed of small (∼100 amino acids) proteins with a conserved primary structure known as the BMC domain. Proteins that contain BMC domains were shown to form hexamers that assemble in layers to form the facets of BMC shells. Previous structural models of the carboxysome shell were built from proteins which contain a single BMC domain. Recently, a new carboxysome shell protein was detected bioinformatically in Prochlorococcus and Synechococcus species. The crystal structure of this protein, CsoS1D, unexpectedly was the first tandem BMC domain protein structurally characterized. These data, together with the transcriptomic evidence suggested that CsoS1D is a novel alpha-carboxysome shell protein with unique functionally important features. Here we used bioinformatic and comparative structural modeling to show that a hypothetical protein found in all beta cyanobacterial genomes is the ortholog of CsoS1D. We also discuss observations of other tandem BMC domain proteins, and we propose the hypothesis that the carboxysome shell may be a dynamic structure that responds to the environmental conditions within the cell.