Reversible and specific extracellular antagonism of receptor-histidine kinase signaling

Gholson J. Lyon, Jesse S. Wright, Arthur Christopoulos, Richard P. Novick, Tom W. Muir

Research output: Contribution to journalArticle

71 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6247-6253
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number8
DOIs
StatePublished - Feb 22 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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