期刊论文详细信息
BMC Systems Biology
Reconstruction and modeling protein translocation and compartmentalization in Escherichia coli at the genome-scale
Adam M Feist1  Bernhard O Palsson1  Karsten Zengler1  Joshua A Lerman2  Edward J O’Brien2  Joanne K Liu2 
[1] Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark;Bioinformatics and Systems Biology, University of California San Diego, 9500 Gilman Drive, Dept. 0419, La Jolla 92093, CA, USA
关键词: compartmentalization;    protein translocation;    metabolism;    gene expression;    Constraint-based modeling;   
Others  :  1126944
DOI  :  10.1186/s12918-014-0110-6
 received in 2014-05-23, accepted in 2014-09-03,  发布年份 2014
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【 摘 要 】

Background

Membranes play a crucial role in cellular functions. Membranes provide a physical barrier, control the trafficking of substances entering and leaving the cell, and are a major determinant of cellular ultra-structure. In addition, components embedded within the membrane participate in cell signaling, energy transduction, and other critical cellular functions. All these processes must share the limited space in the membrane; thus it represents a notable constraint on cellular functions. Membrane- and location-based processes have not yet been reconstructed and explicitly integrated into genome-scale models.

Results

The recent genome-scale model of metabolism and protein expression in Escherichia coli (called a ME-model) computes the complete composition of the proteome required to perform whole cell functions. Here we expand the ME-model to include (1) a reconstruction of protein translocation pathways, (2) assignment of all cellular proteins to one of four compartments (cytoplasm, inner membrane, periplasm, and outer membrane) and a translocation pathway, (3) experimentally determined translocase catalytic and porin diffusion rates, and (4) a novel membrane constraint that reflects cell morphology. Comparison of computations performed with this expanded ME-model, named iJL1678-ME, against available experimental data reveals that the model accurately describes translocation pathway expression and the functional proteome by compartmentalized mass.

Conclusion

iJL1678-ME enables the computation of cellular phenotypes through an integrated computation of proteome composition, abundance, and activity in four cellular compartments (cytoplasm, periplasm, inner and outer membrane). Reconstruction and validation of the model has demonstrated that the iJL1678-ME is capable of capturing the functional content of membranes, cellular compartment-specific composition, and that it can be utilized to examine the effect of perturbing an expanded set of network components. iJL1678-ME takes a notable step towards the inclusion of cellular ultra-structure in genome-scale models.

【 授权许可】

   
2014 Liu et al.; licensee BioMed Central Ltd.

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