Molecular basis of the biogenesis of a protein organelle for ethanolamine utilization.

Abstract

Many pathogenic bacteria use proteinaceous ethanolamine utilization microcompartments (Eut BMCs) to catabolize ethanolamine. This ability gives pathogens a competitive edge over commensal microbiota, which can drive virulence in the inflamed gut. Despite such a critical function, the molecular mechanisms underlying the synthesis of Eut BMCs remain elusive. We report a systematic study for dissecting the molecular basis underlying Eut BMC assembly in <i>Salmonella</i>. We determined the functions of individual constituent proteins in the structure and function of Eut BMCs and demonstrated that EutQ is essential for cargo encapsulation and Eut BMC formation through specific association with the shell and cargo enzymes. We found that Eut proteins can self-assemble to form cargo and shell aggregates independently in vivo and that the biogenesis of Eut BMCs follows a "shell-initiated" pathway. Cargo enzymes exhibit dynamic liquid-like organization within the Eut BMC. Our findings provide mechanistic insights into the structure and assembly of the Eut BMC that serves as a paradigm for membraneless organelles.