Rewiring the specificity of two-component signal transduction systems
| Autor: | Mark Goulian, Orr Ashenberg, Emma A. Lubin, Albert Siryaporn, Barrett S. Perchuk, Michael T. Laub, Jeffrey M. Skerker |
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| Rok vydání: | 2008 |
| Předmět: |
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Molecular MICROBIO Recombinant Fusion Proteins Molecular Sequence Data Regulator Computational biology Biology Protein Engineering General Biochemistry Genetics and Molecular Biology Substrate Specificity Protein structure Bacterial Proteins Multienzyme Complexes Caulobacter crescentus Genes Regulator Escherichia coli Amino Acid Sequence Phosphorylation Peptide sequence Genetics Biochemistry Genetics and Molecular Biology(all) Escherichia coli Proteins Protein engineering Protein Structure Tertiary Crosstalk (biology) SIGNALING Mutagenesis Trans-Activators Signal transduction Bacterial Outer Membrane Proteins Signal Transduction |
| Zdroj: | Cell. 133(6) |
| ISSN: | 1097-4172 |
| Popis: | SummaryTwo-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. |
| Databáze: | OpenAIRE |
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