Annotation inferences using phylogenetic trees
Pseudomonas aeruginosa inhibits endocytic recycling of CFTR in polarized human airway epithelial cells.
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A cell-free filtrate of P. aeruginosa reduced CFTR-mediated transepithelial chloride secretion by inhibiting endocytic recycling of CFTR; the responsible protein was not identified in this study.
"report herein that a cell-free filtrate of P. aeruginosa reduced CFTR-mediated"
Crystal structure of the cystic fibrosis transmembrane conductance regulator inhibitory factor Cif reveals novel active-site features of an epoxide hydrolase virulence factor.
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The 1.8 A structure of Cif shows the epoxide hydrolase catalytic triad Asp129-His297-Glu153, with Asp129 as the nucleophile that opens the epoxide ring.
"Cif has a catalytic triad consisting of residues Asp129, His297, and Glu153"
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Purified Cif hydrolyses epibromohydrin (0.25 U/mg) and cis-stilbene oxide, with a narrow substrate range, and has neither haloacetate nor haloalkane dehalogenase activity.
"Cif does not exhibit activity as either a haloacetate dehalogenase or a haloalkane dehalogenase"
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The authors conclude that the effect of Cif on host CFTR requires hydrolysis of an extended endogenous epoxide substrate, which remains unidentified.
"Cif's effect on host-cell CFTR expression requires the hydrolysis of an extended endogenous epoxide substrate"
The Pseudomonas aeruginosa secreted protein PA2934 decreases apical membrane expression of the cystic fibrosis transmembrane conductance regulator.
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PA2934 is the secreted factor that reduces apical-membrane CFTR; purified His-tagged Cif is necessary and sufficient for the reduction in CFTR and in CFTR-mediated chloride secretion, and the activity requires the conserved catalytic histidine.
"sufficient to mediate the reduction in apical membrane expression of CFTR and a"
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Cif is secreted and associates with outer-membrane-derived vesicles, and cif is expressed in the cystic fibrosis lung.
"is a secreted protein and is found associated with outer membrane-derived"
A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
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Cif, delivered in outer-membrane vesicles, redirects endocytosed CFTR from recycling endosomes to lysosomes by stabilising G3BP1-mediated inhibition of the deubiquitinase USP10, increasing CFTR ubiquitination and lysosomal degradation.
"Cif redirected endocytosed CFTR from recycling endosomes to lysosomes by"
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Outer-membrane vesicles from P. aeruginosa lacking Cif had no effect on CFTR, so the trafficking change is attributable to Cif.
"Cif redirects CFTR from recycling endosomes to the lysosomal, degradative pathway"
UniProt entry Q9HZR3 (cif, PA2934)