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Issue 11, 2011
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Patterns of indirect protein interactions suggest a spatial organization to metabolism

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Abstract

It has long been believed that cells organize their cytoplasm so as to efficiently channel metabolites between sequential enzymes. This metabolic channeling has the potential to yield higher metabolic fluxes as well as better regulatory control over metabolism. One mechanism for achieving such channeling is to ensure that sequential enzymes in a pathway are physically close to each other in the cell. We present evidence that indirect protein interactions between related enzymes represent a global mechanism for achieving metabolic channeling; the intuition being that protein interactions between enzymes and non-enzymatic mediator proteins are a powerful means of physically associating enzymes in a modular fashion. By analyzing the metabolic and proteinprotein interactions networks of Escherichia coli, yeast and humans, we are able to show that all three species have many more indirect protein interactions linking enzymes that share metabolites than would be expected by chance. Moreover, these interactions are distributed non-randomly in the metabolic network. Our analyses in yeast and E. coli show that reactions possessing such interactions also show higher flux than do those lacking them. On the basis of these observations, we suggest that an important role of protein interactions with mediator proteins is to contribute to the spatial organization of the cell. This hypothesis is supported by the fact that these mediator proteins are also enriched with annotations related to signal transduction, a system where scaffolding proteins are known to limit cross-talk by controlling spatial localization.

Graphical abstract: Patterns of indirect protein interactions suggest a spatial organization to metabolism

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Publication details

The article was received on 05 May 2011, accepted on 08 Aug 2011 and first published on 31 Aug 2011


Article type: Paper
DOI: 10.1039/C1MB05168G
Citation: Mol. BioSyst., 2011,7, 3056-3064
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    Patterns of indirect protein interactions suggest a spatial organization to metabolism

    Å. Pérez-Bercoff, A. McLysaght and G. C. Conant, Mol. BioSyst., 2011, 7, 3056
    DOI: 10.1039/C1MB05168G

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