title: Regulatory interactions between a bacterial tyrosine kinase and its cognate phosphatase.
abstract: The cyclic process of autophosphorylation of the C-terminal tyrosine cluster (YC) of a bacterial tyrosine kinase and its subsequent dephosphorylation following interactions with a counteracting tyrosine phosphatase regulates diverse physiological processes, including the biosynthesis and export of polysaccharides responsible for the formation of biofilms or virulence-determining capsules. We provide here the first detailed insight into this hitherto uncharacterized regulatory interaction at residue-specific resolution using Escherichia coli Wzc, a canonical bacterial tyrosine kinase, and its opposing tyrosine phosphatase, Wzb. The phosphatase Wzb utilizes a surface distal to the catalytic elements of the kinase, Wzc, to dock onto its catalytic domain (WzcCD). WzcCD binds in a largely YC-independent fashion near the Wzb catalytic site, inducing allosteric changes therein. YC dephosphorylation is proximity-mediated and reliant on the elevated concentration of phosphorylated YC near the Wzb active site resulting from WzcCD docking. Wzb principally recognizes the phosphate of its phosphotyrosine substrate and further stabilizes the tyrosine moiety through ring stacking interactions with a conserved active site tyrosine.
authors.affiliation: Department of Chemistry, City College of New York, New York, New York 10031, USA.
authors.forename: Deniz B
authors.initials: DB
authors.lastname: Temel
authors.forename: Kaushik
authors.initials: K
authors.lastname: Dutta
authors.forename: Sébastien
authors.initials: S
authors.lastname: Alphonse
authors.forename: Julien
authors.initials: J
authors.lastname: Nourikyan
authors.forename: Christophe
authors.initials: C
authors.lastname: Grangeasse
authors.forename: Ranajeet
authors.initials: R
authors.lastname: Ghose
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D020134:Catalytic Domain; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D019000:Phosphotyrosine / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C499615:wzc protein, E coli; D010749:Phosphoprotein Phosphatases; C428435:Wzb protein, E coli
keywords: NMR; Prokaryotic Signal Transduction; Protein-Protein Interactions; Protein-tyrosine Kinase (Tyrosine Kinase); Protein-tyrosine Phosphatase (Tyrosine Phosphatase)
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