Metabolic adaptation and protein complexes in prokaryotes

Abstract

Protein complexes are classified and have been charted in several large-scale screening studies in prokaryotes. These complexes are organized in a factory-like fashion to optimize protein production and metabolism. Central components are conserved between different prokaryotes; major complexes involve carbohydrate, amino acid, fatty acid and nucleotide metabolism. Metabolic adaptation changes protein complexes according to environmental conditions. Protein modification depends on specific modifying enzymes. Proteins such as trigger enzymes display condition-dependent adaptation to different functions by participating in several complexes. Several bacterial pathogens adapt rapidly to intracellular survival with concomitant changes in protein complexes in central metabolism and optimize utilization of their favorite available nutrient source. Regulation optimizes protein costs. Master regulators lead to up- and downregulation in specific subnetworks and all involved complexes. Long protein half-life and low level expression detaches protein levels from gene expression levels. However, under optimal growth conditions, metabolite fluxes through central carbohydrate pathways correlate well with gene expression. In a system-wide view, major metabolic changes lead to rapid adaptation of complexes and feedback or feedforward regulation. Finally, prokaryotic enzyme complexes are involved in crowding and substrate channeling. This depends on detailed structural interactions and is verified for specific effects by experiments and simulations.

Figure 1

Proteins and complexes.

Figure 2

Protein complexes and their connection with metabolism. A number of central complexes are shown, giving the situation in E. coli, as well as implied and connected central metabolic pathways. In S. aureus, details of several complexes differ (E. coli-specific complexes not present in S. aureus are labeled with E (in green), S. aureus-specific complexes not present in E. coli are labeled with S in yellow, see text). For details see text. Abbreviations: Ac-Coa, acetyl-CoA; Fru-1,6, fructose-1,6-bisphosphate, Fru-6P, fructose 6-phosphate; Glu, glucose; Glu-6P, glucose 6-phosphate; Gnt-6P, 6-phospho gluconate; PEP, phosphoenolpyruvate; PPP, pentose phosphate pathway; PTS, phosphotransferase system; Pyr, pyruvate; TCA, tricarboxylic acid; TriP, triose phosphate.

Figure 3

(a) Substrate channeling. Originally a conveyor belt concept was invoked (left): Substrate (arrows) is passed from one enzyme to the next (squares in different grey shades). A more modern view (right) considers complexes central for channeling and places the protein complex in the middle, substrates change and are passed around (arrows), furthermore, super-complexes (grey ellipsoid in the background) unite different complexes for even more efficient channeling; (b) Molecular crowding. A large molecule (long shape, left) cannot freely move if some obstacles are present (proteins shown as spheres). The effect becomes more pronounced (right) with diverse and more protein species present (different spheres and shades).