Reversible and specific extracellular antagonism of receptor-histidine kinase signaling

Lyon, Gholson J., Wright, Jesse S., Christopoulos, Arthur, Novick, Richard P., Muir, Tom W. (2002) Reversible and specific extracellular antagonism of receptor-histidine kinase signaling. Journal of Biological Chemistry, 277 (8). pp. 6247-6253. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/11733525
DOI: 10.1074/jbc.M109989200

Abstract

Staphylococcal pathogenesis is regulated by a two-component quorum-sensing system, agr, activated by a self-coded autoinducing peptide (AIP). The agr system is widely divergent and is unique in that variant AIPs cross-inhibit agr activation in heterologous combinations. Cross-inhibition, but not self-activation, is widely tolerant of structural diversity in the AIPs so that these two processes must involve different mechanisms of interaction with the respective receptors. Herein, we have utilized this naturally occurring antagonism to demonstrate that both activation and inhibition are reversible and that activators and inhibitors interact at a common site on the receptor. These results suggest that molecules designed to compete with natural agonists for binding at receptor-histidine kinase sensor domains could represent a general approach to the inhibition of receptor-histidine kinase signaling.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Bacterial Proteins Genetic Variation Kinetics Protein Conformation Protein Kinase Inhibitors Protein Kinases Receptors, Cell Surface Recombinant Fusion Proteins Signal Transduction Staphylococcus aureus Trans-Activators
Subjects: organism description > bacteria
CSHL Authors:
Communities: CSHL labs > Lyon lab
Depositing User: Matt Covey
Date Deposited: 10 Dec 2012 20:13
Last Modified: 10 Dec 2012 21:21
URI: http://repository.cshl.edu/id/eprint/26280

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