Symmetric Signaling within Asymmetric Dimers of the Staphylococcus aureus Receptor Histidine Kinase AgrC. Export

@article{citeulike:5757684, abstract = {SUMMARY Virulence in Staphylococcus aureus is largely under control of the accessory gene regulator (agr) quorum sensing system. The AgrC receptor histidine kinase detects its autoinducing peptide (AIP) ligand and generates an intracellular signal resulting in secretion of virulence factors. Although agr is a well-studied quorum sensing system, little is known about the mechanism of AgrC activation. By co-immunoprecipitation analysis and intermolecular complementation of receptor mutants, we showed that AgrC forms ligand-independent dimers that undergo trans-autophosphorylation upon interaction with AIP. Remarkably, addition of specific AIPs to AgrC mutant dimers with only one functional sensor domain caused symmetric activation of either kinase domain despite the sensor asymmetry. Furthermore, mutant dimers involving one constitutive protomer demonstrated ligand-independent activity, irrespective of which protomer was kinase deficient. These results demonstrate that signaling through either individual AgrC protomer causes symmetric activation of both kinase domains. We suggest that such signaling across the dimer interface may be an important mechanism for dimeric quorum sensing receptors to rapidly elicit a response upon signal detection.}, author = {George Cisar, Elizabeth A. and Geisinger, Edward and Muir, Tom W. and Novick, Richard P.}, citeulike-article-id = {5757684}, citeulike-linkout-0 = {http://dx.doi.org/10.1111/j.1365-2958.2009.06849.x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19708918}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19708918}, day = {24}, doi = {10.1111/j.1365-2958.2009.06849.x}, issn = {1365-2958}, journal = {Molecular microbiology}, keywords = {agrc, asymmetric, aureus, dimers, histidine, kinase, receptor, signaling, staphylococcus, symmetric}, month = {August}, posted-at = {2009-09-09 11:03:16}, priority = {2}, title = {Symmetric Signaling within Asymmetric Dimers of the Staphylococcus aureus Receptor Histidine Kinase AgrC.}, url = {http://dx.doi.org/10.1111/j.1365-2958.2009.06849.x}, year = {2009} }

TY - JOUR ID - citeulike:5757684 L3 - citeulike-article-id:5757684 N2 - SUMMARY Virulence in Staphylococcus aureus is largely under control of the accessory gene regulator (agr) quorum sensing system. The AgrC receptor histidine kinase detects its autoinducing peptide (AIP) ligand and generates an intracellular signal resulting in secretion of virulence factors. Although agr is a well-studied quorum sensing system, little is known about the mechanism of AgrC activation. By co-immunoprecipitation analysis and intermolecular complementation of receptor mutants, we showed that AgrC forms ligand-independent dimers that undergo trans-autophosphorylation upon interaction with AIP. Remarkably, addition of specific AIPs to AgrC mutant dimers with only one functional sensor domain caused symmetric activation of either kinase domain despite the sensor asymmetry. Furthermore, mutant dimers involving one constitutive protomer demonstrated ligand-independent activity, irrespective of which protomer was kinase deficient. These results demonstrate that signaling through either individual AgrC protomer causes symmetric activation of both kinase domains. We suggest that such signaling across the dimer interface may be an important mechanism for dimeric quorum sensing receptors to rapidly elicit a response upon signal detection. JF - Molecular microbiology SN - 1365-2958 TI - Symmetric Signaling within Asymmetric Dimers of the Staphylococcus aureus Receptor Histidine Kinase AgrC. KW - agrc KW - asymmetric KW - aureus KW - dimers KW - histidine KW - kinase KW - receptor KW - signaling KW - staphylococcus KW - symmetric AU - George Cisar, Elizabeth AU - Geisinger, Edward AU - Muir, Tom AU - Novick, Richard PY - 2009/08/24/ UR - http://dx.doi.org/10.1111/j.1365-2958.2009.06849.x ER -