Two-component signal transduction systems are the predominant means by which bacteria sense and respond to environmental stimuli. Bacteria often employ tens or hundreds of these paralogous signaling systems, comprised of histidine kinases (HKs) and their cognate response regulators (RRs). Faithful transmission of information through these signaling pathways and avoidance of detrimental crosstalk demand exquisite specificity of HK-RR interactions. To identify the determinants of two-component signaling specificity, we examined patterns of amino acid coevolution in large, multiple sequence alignments of cognate kinase-regulator pairs. Guided by these results, we demonstrate that a subset of the coevolving residues is sufficient, when mutated, to completely switch the substrate specificity of the kinase EnvZ. Our results shed light on the basis of molecular discrimination in two-component signaling pathways, provide a general approach for the rational rewiring of these pathways, and suggest that analyses of coevolution may facilitate the reprogramming of other signaling systems and protein-protein interactions.
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| http://dx.doi.org/10.1016/j.cell.2008.04.040 | DOI Listing |
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Article Synopsis
- Signal transduction is key for communication and response in microbial communities, allowing them to adapt to environmental changes and establish structures for collective behaviors.
- Microbial communication occurs through methods like quorum sensing, biofilm formation, and chemotaxis, which help coordinate activities, enhance resource use, and improve resilience against stress.
- Understanding these signaling processes, especially in synthetic microbial consortia, has important implications for biotechnology, including biosensors, biodegradation, and waste management.
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