Exploring Dynamic Events of Bacterial Microcompartment Shell Pores

Abstract

Bacterial Microcompartments (BMCs) are proteinaceous organelles that sequester key metabolic reactions to increase enzymatic efficiency and prevent the loss of volatile or cytotoxic intermediates. 7 distinct BMC-type operons have been identified in 20-25% of bacteria, including BMCs involved in carbon fixation, propanediol catabolism, and ethanolamine catabolism. Ranging from 100 to 150 nm in width, BMCs are encapsulated in a protein shell consisting of hexagonal tiles of the conserved BMC-fold proteins. The BMC-fold proteins homo-oligomerize into hexameric or pseudo-hexameric assemblies with unique functionalities. High resolution X-ray determined structures have previously elucidated the organization and tiling interactions of several shell proteins from BMCs. However, it remains unknown how small molecule metabolites may enter or exit the BMC, passing through the protein shell; nor how intermediates may be trapped inside. Here, we present initial findings using current methods in Molecular Dynamics to investigate BMC shell pores, including: (1) Metadynamics and Umbrella Sampling to probe the free energy profile of small molecule metabolites at predicted routes through BMC shell protein hexamer pores; (2) Accelerated MD and Targeted MD to observe the conformational change between BMC shell protein pseudo-hexamers that have been solved in open and closed pore conformations. These experiments shed insight on BMC shell pore dynamics and function, furthering our understanding of BMC systems.