Receptor methylation controls the magnitude of stimulus-response coupling in bacterial chemotaxis.
Motile prokaryotes employ a chemoreceptor-kinase array to sense changes in the media and properly adjust their swimming behavior. This array is composed of a family of Type I membrane receptors, a histidine protein kinase (CheA), and an Src homology 3-like protein (CheW). Binding of an attractant to the chemoreceptors inhibits CheA, which results in decreased phosphorylation of the chemotaxis response regulator (CheY). Sensitivity of the system to stimuli is modulated by a protein methyltransferase (CheR) and a protein methylesterase (CheB) that catalyze the methylation and demethylation of specific glutamyl residues in the cytoplasmic domain of the receptors. One of the most fundamental unanswered questions concerning the bacterial chemotaxis mechanism is the quantitative relationship between ligand binding to receptors and CheA inhibition. We show that the receptor glutamyl modifications cause adaptation by changing the gain (magnitude amplification) between attractant binding and kinase inhibition without substantially affecting ligand binding affinity. The mechanism adjusts receptor sensitivity to background stimulus intensity over several orders of magnitude of attractant concentrations. The cooperative effects of ligand binding appear to be minimal with Hill coefficients for kinase inhibition less than 2, independent of the state of glutamyl modification.
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Mikhail N
MN
Levit
Jeffry B
JB
Stock
D001426:Bacterial Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D000072236:Methyl-Accepting Chemotaxis Proteins; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D011485:Protein Binding; D012486:Salmonella typhimurium / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
D001426:Bacterial Proteins; D008024:Ligands; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; C051236:CheW protein, Bacteria; D018698:Glutamic Acid; D012694:Serine; D008780:Methyltransferases; C038706:chemotaxis methyltransferase