Bacterial microcompartments: their properties and paradoxes

Abstract

Many bacteria conditionally express proteinaceous organelles referred to here as microcompartments (Fig. 1). These microcompartments are thought to be involved in a least seven different metabolic processes and the number is growing. Microcompartments are very large and structurally sophisticated. They are usually about 100-150 nm in cross section and consist of 10,000-20,000 polypeptides of 10-20 types. Their unifying feature is a solid shell constructed from proteins having bacterial microcompartment (BMC) domains. In the examples that have been studied, the microcompartment shell encases sequentially acting metabolic enzymes that catalyze a reaction sequence having a toxic or volatile intermediate product. It is thought that the shell of the microcompartment confines such intermediates, thereby enhancing metabolic efficiency and/or protecting cytoplasmic components. Mechanistically, however, this creates a paradox. How do microcompartments allow enzyme substrates, products and cofactors to pass while confining metabolic intermediates in the absence of a selectively permeable membrane? We suggest that the answer to this paradox may have broad implications with respect to our understanding of the fundamental properties of biological protein sheets including microcompartment shells, S-layers and viral capsids.

Figure 1

Electron micrograph of bacterial microcompartments: a: The carboxysomes of H. neapolitanus; b: The organelles formed during growth of Salmonella enterica on 1,2-propanediol. Triangles point to the microcompartments.

Figure 2

The bacterial carbon dioxide concentrating mechanism. a: The bacterial CCM starts with transport of inorganic carbon into the cell as HCO₃⁻. Equilibrium between HCO₃⁻ and CO₂ is not reached due to a lack of carbonic anhydrase in the cytoplasm. HCO₃⁻ is converted to CO₂ by carboxysomal carbonic anhydrase within the microcompartment lumen. The protein shell of the carboxysome impedes CO₂ diffusion. Consequently, CO₂ can accumulate in the immediate vicinity of RuBisCO while diffusive loss of CO₂ through the cell membrane is minimized. Elevated CO₂ proximal to RuBisCO increases carbon fixation and suppresses photorespiration (a nonproductive process in which O₂ replaces CO₂ as a substrate for RuBisCO). b: A preliminary atomic model of the carboxysome shell based on crystal structures of the component shell proteins.⁽¹²⁾ The positively charged pores through the sheet of hexagonal proteins are indicated. These have been postulated to enhance the diffusion of negatively charged molecules such as bicarbonate (thick arrow) across the shell, compared to uncharged molecules such as CO₂ and O₂ (thin arrows).

Figure 3

Model for 1,2-propanediol degradation by S. enterica. The dashed line indicates the shell of the microcompartment which is composed of seven BMC-domain proteins (PduABB′JKTU). The first two steps of 1,2-propanediol degradation (conversion of 1,2-propanediol to propionyl-CoA) occur in the lumen of the microcompartment and the remaining steps in the cytoplasm. The proposed function of this microcompartment is sequestration of propionaldehyde to minimize its toxicity. The Ado-B₁₂ cofactor is sometimes converted to B₁₂(III) in a catalytic by-reaction inactivating diol dehydratase. B₁₂(III) is released from diol dehydratase (PduCDE) by a reactivase (PduGH), and reduced to B₁₂(I) by an unknown enzyme. Then, ATP:cob(I)alamin adenosyltransferase (PduO) converts B₁₂(I) to active cofactor (Ado-B₁₂) which associateswith diol dehydratase to form active holoenzyme. Abbreviations: 1,2-PD, 1,2-propanediol; PduCDE, coenzyme B₁₂-dependent diol dehydratase; PduP, propionaldehyde dehydrogenase; PduL, phosphotransacylase; PduW, propionate kinase; PduQ, 1-propanol dehydrogenase.

Figure 4

Purified Pdu microcompartments.