The Structure of CcmP, a Tandem Bacterial Microcompartment Domain Protein from the β-Carboxysome, Forms a Subcompartment Within a Microcompartment

• Published in: The Journal of biological chemistry Vol. 288; no. 22; pp. 16055 - 16063
• Main Authors: Cai, Fei, Sutter, Markus, Cameron, Jeffrey C., Stanley, Desiree N., Kinney, James N., Kerfeld, Cheryl A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.05.2013; American Society for Biochemistry and Molecular Biology
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Carbon Dioxide; Carboxysome; Cell Compartmentation; CO2 Fixation; Genome, Bacterial - physiology; Glyceric Acids - chemistry; Glyceric Acids - metabolism; Microbiology; Microcompartment; Multigene Family - physiology; Protein Multimerization - physiology; Protein Self-assembly; Protein Structure; Protein Structure and Folding; Protein Structure, Quaternary; Protein Structure, Tertiary; Synechococcus - chemistry; Synechococcus - genetics; Synechococcus - metabolism; Cell Compartmentation; CO2 Fixation; Protein Self-assembly; Microcompartment; Microbiology; Carboxysome; Protein Structure; Carbon Dioxide
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.M113.456897

The carboxysome is a bacterial organelle found in all cyanobacteria; it encapsulates CO2 fixation enzymes within a protein shell. The most abundant carboxysome shell protein contains a single bacterial microcompartment (BMC) domain. We present in vivo evidence that a hypothetical protein (dubbed CcmP) encoded in all β-cyanobacterial genomes is part of the carboxysome. We show that CcmP is a tandem BMC domain protein, the first to be structurally characterized from a β-carboxysome. CcmP forms a dimer of tightly stacked trimers, resulting in a nanocompartment-containing shell protein that may weakly bind 3-phosphoglycerate, the product of CO2 fixation. The trimers have a large central pore through which metabolites presumably pass into the carboxysome. Conserved residues surrounding the pore have alternate side-chain conformations suggesting that it can be open or closed. Furthermore, CcmP and its orthologs in α-cyanobacterial genomes form a distinct clade of shell proteins. Members of this subgroup are also found in numerous heterotrophic BMC-associated gene clusters encoding functionally diverse bacterial organelles, suggesting that the potential to form a nanocompartment within a microcompartment shell is widespread. Given that carboxysomes and architecturally related bacterial organelles are the subject of intense interest for applications in synthetic biology/metabolic engineering, our results describe a new type of building block with which to functionalize BMC shells. Background: CcmP is a hypothetical protein conserved among all β-cyanobacteria. Results: CcmP is a β-carboxysome component; it forms a bilayered shell protein. Conclusion: CcmP may facilitate flux of larger metabolites across the carboxysome shell. Significance: It is the first structure of a β-carboxysome tandem BMC domain protein; phylogenetically, it represents a new type of microcompartment building block.