AgrC sensor histidine kinase (AgrC)

AgrC sensor histidine kinase is a 430-amino acid integral membrane protein found in *Staphylococcus aureus* that acts as the sensor half of the archetypal bacterial two-component quorum sensing system (Agr system). AgrC detects extracellular autoinducing peptides (AIPs), which signal when the bacterial population has reached a critical density. Upon AIP binding, AgrC dimerizes and autophosphorylates a conserved histidine in its cytoplasmic domain, then transfers this phosphate to the response regulator AgrA. The AgrA activation initiates changes in gene expression, notably upregulating virulence factors crucial for infection. The AgrC-AgrA pathway’s activity can be modulated by peptide agonists (which activate) and specific inhibitors or inverse agonists (which suppress or block) through distinct conformational changes of the receptor. There are various natural and synthetic AIP variants, and different allelic versions of AgrC/AIP interact to produce activating or inhibitory effects, which underlie a form of bacterial communication and competition ("quorum sensing interference")[1][2][4][6][7]. AgrC is considered a promising antimicrobial target for reducing virulence rather than directly killing bacteria. Key structural and mechanistic notes: - AgrC consists of a multi-helix transmembrane sensor domain and a cytoplasmic histidine kinase domain connected by a helical linker[1][3][6]. - Ligand binding induces specific helical movements and conformational states, leading to either activation or inhibition of kinase function[1][4]. - The specificity for the response regulator (AgrA) is tightly governed by sequence and structural features at the kinase-regulator interface[5].

Other names

AgrCStaphylococcus aureus AgrCAgrC sensor kinaseAgrC receptor

Peptide agonists (AIPs) bind to AgrC, induce autophosphorylation, and activate AgrA via phosphotransfer Peptide antagonists/inverse agonists bind to AgrC, inhibit phosphorylation, and block quorum sensing activation[1][4][7]