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Identification of a Distinct Substrate-binding Domain in the Bacterial Cysteine Methyltransferase Effectors NleE and OspZ.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2016 Sep 16; Vol. 291 (38), pp. 20149-62. Date of Electronic Publication: 2016 Jul 21. - Publication Year :
- 2016
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Abstract
- The type III secretion system effector protein NleE from enteropathogenic Escherichia coli plays a key role in the inhibition of NF-κB activation during infection. NleE inactivates the ubiquitin chain binding activity of host proteins TAK1-binding proteins 2 and 3 (TAB2 and TAB3) by modifying the Npl4 zinc finger domain through S-adenosyl methionine-dependent cysteine methylation. Using yeast two-hybrid protein interaction studies, we found that a conserved region between amino acids 34 and 52 of NleE, in particular the motif (49)GITR(52), was critical for TAB2 and TAB3 binding. NleE mutants lacking (49)GITR(52) were unable to methylate TAB3, and wild type NleE but not NleE(49AAAA52) where each of GITR was replaced with alanine restored the ability of an nleE mutant to inhibit IL-8 production during infection. Another NleE target, ZRANB3, also associated with NleE through the (49)GITR(52) motif. Ectopic expression of an N-terminal fragment of NleE (NleE(34-52)) in HeLa cells showed competitive inhibition of wild type NleE in the suppression of IL-8 secretion during enteropathogenic E. coli infection. Similar results were observed for the NleE homologue OspZ from Shigella flexneri 6 that also bound TAB3 through the (49)GITR(52) motif and decreased IL-8 transcription through modification of TAB3. In summary, we have identified a unique substrate-binding motif in NleE and OspZ that is required for the ability to inhibit the host inflammatory response.<br /> (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Amino Acid Motifs
DNA Helicases genetics
Dysentery, Bacillary genetics
Enteropathogenic Escherichia coli genetics
Escherichia coli Infections genetics
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins genetics
Protein Binding
Shigella flexneri genetics
Adaptor Proteins, Signal Transducing metabolism
DNA Helicases metabolism
Dysentery, Bacillary metabolism
Enteropathogenic Escherichia coli metabolism
Escherichia coli Infections metabolism
Escherichia coli Proteins metabolism
Intracellular Signaling Peptides and Proteins metabolism
Shigella flexneri metabolism
Virulence Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 291
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 27445336
- Full Text :
- https://doi.org/10.1074/jbc.M116.734079