Duplication of genes in an ATP-binding cassette transport system increases dynamic range while maintaining ligand specificity.

Sudipa Ghimire-Rijal, Xun Lu, Dean A Myles, Matthew J Cuneo

The Journal of biological chemistry 2014 Oct 24

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Many bacteria exist in a state of feast or famine where high nutrient availability leads to periods of growth followed by nutrient scarcity and growth stagnation. To adapt to the constantly changing nutrient flux, metabolite acquisition systems must be able to function over a broad range. This, however, creates difficulties as nutrient concentrations vary over many orders of magnitude, requiring metabolite acquisition systems to simultaneously balance ligand specificity and the dynamic range in which a response to a metabolite is elicited. Here we present how a gene duplication of a periplasmic binding protein in a mannose ATP-binding cassette transport system potentially resolves this dilemma through gene functionalization. Determination of ligand binding affinities and specificities of the gene duplicates with fluorescence and circular dichroism demonstrates that although the binding specificity is maintained the Kd values for the same ligand differ over three orders of magnitude. These results suggest that this metabolite acquisition system can transport ligand at both low and high environmental concentrations while preventing saturation with related and less preferentially metabolized compounds. The x-ray crystal structures of the β-mannose-bound proteins help clarify the structural basis of gene functionalization and reveal that affinity and specificity are potentially encoded in different regions of the binding site. These studies suggest a possible functional role and adaptive advantage for the presence of two periplasmic-binding proteins in ATP-binding cassette transport systems and a way bacteria can adapt to varying nutrient flux through functionalization of gene duplicates. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Citation

Sudipa Ghimire-Rijal, Xun Lu, Dean A Myles, Matthew J Cuneo. Duplication of genes in an ATP-binding cassette transport system increases dynamic range while maintaining ligand specificity. The Journal of biological chemistry. 2014 Oct 24;289(43):30090-100