Rewiring the specificity of two-component signal transduction systems. Export

@article{citeulike:2910599, abstract = {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.}, address = {Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.}, author = {Skerker, Jeffrey M. and Perchuk, Barrett S. and Siryaporn, Albert and Lubin, Emma A. and Ashenberg, Orr and Goulian, Mark and Laub, Michael T.}, citeulike-article-id = {2910599}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2008.04.040}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0092867408006144}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18555780}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18555780}, day = {13}, doi = {10.1016/j.cell.2008.04.040}, issn = {1097-4172}, journal = {Cell}, keywords = {correlation, method, mutation, network, protein, signal, transduction}, month = {Jun}, number = {6}, pages = {1043--1054}, posted-at = {2009-08-15 15:24:14}, priority = {2}, title = {Rewiring the specificity of two-component signal transduction systems.}, url = {http://dx.doi.org/10.1016/j.cell.2008.04.040}, volume = {133}, year = {2008} }

TY - JOUR ID - citeulike:2910599 L3 - citeulike-article-id:2910599 N2 - 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. IS - 6 JF - Cell SN - 1097-4172 AD - Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. EP - 1054 TI - Rewiring the specificity of two-component signal transduction systems. VL - 133 SP - 1043 KW - correlation KW - method KW - mutation KW - network KW - protein KW - signal KW - transduction AU - Skerker, Jeffrey AU - Perchuk, Barrett AU - Siryaporn, Albert AU - Lubin, Emma AU - Ashenberg, Orr AU - Goulian, Mark AU - Laub, Michael PY - 2008/Jun/13/ UR - http://dx.doi.org/10.1016/j.cell.2008.04.040 ER -