Krüger Beate, Liang Chunguang, Prell Florian, Fieselmann Astrid, Moya Andres, Schuster Stefan, Völker Uwe, Dandekar Thomas
Department of Bioinformatics, Biocenter, Am Hubland, University of Würzburg, 97074 Würzburg, Germany.
Unidad Mixta de Investigación en Genómica y Salud CSISP-UVEG, University of València José Beltrán 2, 46980 Paterna, Valencia, Spain.
Metabolites. 2012 Nov 16;2(4):940-58. doi: 10.3390/metabo2040940.
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.
蛋白质复合物已在原核生物的多项大规模筛选研究中进行了分类和绘制。这些复合物以工厂化的方式组织起来,以优化蛋白质的生产和代谢。不同原核生物之间的核心成分是保守的;主要复合物涉及碳水化合物、氨基酸、脂肪酸和核苷酸代谢。代谢适应会根据环境条件改变蛋白质复合物。蛋白质修饰取决于特定的修饰酶。诸如触发酶之类的蛋白质通过参与多种复合物而表现出对不同功能的条件依赖性适应。几种细菌病原体通过中心代谢中蛋白质复合物的相应变化迅速适应细胞内存活,并优化对其最喜爱的可用营养源的利用。调控可优化蛋白质成本。主调控因子导致特定子网络及所有相关复合物的上调和下调。蛋白质的长半衰期和低水平表达使蛋白质水平与基因表达水平脱钩。然而,在最佳生长条件下,通过中心碳水化合物途径的代谢物通量与基因表达密切相关。从系统层面来看,主要的代谢变化会导致复合物的快速适应以及反馈或前馈调控。最后,原核生物酶复合物参与拥挤和底物通道化。这取决于详细的结构相互作用,并通过实验和模拟验证了其特定效应。