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Enzyme encapsulation peptides bind to the groove between tessellating subunits of the bacterial microcompartment shell

Bradley-Clarke, J.; Gu, S.; Rose, R. S.; Warren, M. J.; Pickersgill, R. W.

2022-12-30 biochemistry
10.1101/2022.12.30.522206 bioRxiv
Show abstract

Bacterial microcompartments are prokaryotic organelles consisting of encapsulated enzymes within a thin protein shell. They are involved in metabolic processing including propanediol, choline, glycerol and ethanolamine utilization, and carbon fixation. Enzymes targeted to the inside of the microcompartment frequently possess a cargo-encapsulation peptide, but the binding-site has not been revealed. We provide evidence that the encapsulation peptides bind to the hydrophobic groove formed between tessellating tiles of major shell proteins. In silico docking studies provide a compelling model of peptide binding to this hydrophobic groove. This result is consistent with the now widely accepted view that the convex side of the shell proteins faces the lumen of the microcompartment. Binding between shell protein tiles explains why the encapsulation peptide binding site has been elusive, how encapsulation-peptide bearing enzymes can promote shell assembly, and how the presence of cargo affects the size and shape of the bacterial microcompartment.

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