A Receptor-Modifying Deamidase in Complex with a Signaling Phosphatase Reveals Reciprocal Regulation

Abstract

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.

Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

“…Homology searches predicted with high confidence that the C-terminal region (residues 130-284) of HopAF1 from Pto DC3000 is structurally related to CheD, a single-domain chemotaxis protein from Thermotoga maritima (Fig. 1A) (43).…”

“…CheD is a deamidase protein that activates methyl-accepting chemotaxis proteins (43). CheD is structurally related to the cytotoxic necrotizing factor family of bacterial deamidases (44,45).…”

Comparative structural bioinformatics analysis of Bacillus amyloliquefaciens chemotaxis proteins within Bacillus subtilis group

“…3). None of these sites is in close spatial proximity to the N-terminal phosphor binding site or the catalytic triad that consists of S171, H200 and D294 (Djordjevic et al 1998) Binding of CheC to CheD was proved experimentally (Chao et al 2006) (see Fig. 4D).…”

“…1U0S ); 2CH4 , 2F9Z (Chao et al 2006) and 3HZH (Pazy et al 2010). More information on templates can be found in Table 1.…”

“…The homology models of the chemotaxis proteins, CheB, CheC, CheD, CheR, CheW, CheY of B. amyloliquefaciens FZB42 were calculated using available crystal structures of their homologs, obtained from the Protein Data Bank (PDB). The respective templates used were: 1A2O (Djordjevic et al 1998), 1XKR ), 2F9Z (Chao et al 2006), 1AF7 (Djordjevic and Stock 1997), 2QDL (Yao et al 2007), 1TMY (Usher et al 1998) respectively. For further information on target-template matches see Table 1.…”