A receptor-modifying deamidase in complex with a signaling phosphatase reveals reciprocal regulation.
Signal transduction underlying bacterial chemotaxis involves excitatory phosphorylation and feedback control through deamidation and methylation of sensory receptors. The structure of a complex between the signal-terminating phosphatase, CheC, and the receptor-modifying deamidase, CheD, reveals how CheC mimics receptor substrates to inhibit CheD and how CheD stimulates CheC phosphatase activity. CheD resembles other cysteine deamidases from bacterial pathogens that inactivate host Rho-GTPases. CheD not only deamidates receptor glutamine residues contained within a conserved structural motif but also hydrolyzes glutamyl-methyl-esters at select regulatory positions. Substituting Gln into the receptor motif of CheC turns the inhibitor into a CheD substrate. Phospho-CheY, the intracellular signal and CheC target, stabilizes the CheC:CheD complex and reduces availability of CheD. A point mutation that dissociates CheC from CheD impairs chemotaxis in vivo. Thus, CheC incorporates an element of an upstream receptor to influence both its own effect on receptor output and that of its binding partner, CheD.
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Xingjuan
X
Chao
Travis J
TJ
Muff
Sang-Youn
SY
Park
Sheng
S
Zhang
Abiola M
AM
Pollard
George W
GW
Ordal
Alexandrine M
AM
Bilwes
Brian R
BR
Crane
D000581:Amidohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002633:Chemotaxis; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins; D005246:Feedback; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D008958:Models, Molecular; D046912:Multiprotein Complexes; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D046912:Multiprotein Complexes; C000607606:cheY protein, E coli; C000607604:tsr protein, E coli; D010744:Phosphoric Monoester Hydrolases; D000581:Amidohydrolases