The EHEC Type III Effector NleL Is an E3 Ubiquitin Ligase That Modulates Pedestal Formation
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Piscatelli-2011-The EHEC Type III Ef.pdf
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1.49 MB
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Author(s)
Piscatelli, Heather
Kotkar, Shalaka A.
McBee, Megan E.
Muthupalani, Sureshkumar
Schauer, David B.
Mandrell, Robert E.
Leong, John M.
Zhou, Daoguo
Date Issued
April 2011
Journal
PLoS One
Publisher
Public Library of Science
Citation
Piscatelli, Heather et al. “The EHEC Type III Effector NleL Is an E3 Ubiquitin Ligase That Modulates Pedestal Formation.” Ed. F. Gisou van der Goot. PLoS ONE 6.4 (2011) : e19331.
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Final published version
Abstract
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome in humans. EHEC colonize the intestinal mucosa and promote the formation of actin-rich pedestals via translocated type III effectors. Two EHEC type III secreted effectors, Tir and EspFu/TccP, are key players for pedestal formation. We discovered that an EHEC effector protein called Non-LEE-encoded Ligase (NleL) is an E3 ubiquitin ligase. In vitro, we showed that the NleL C753 residue is critical for its E3 ligase activity. Functionally, we demonstrated that NleL E3 ubiquitin ligase activity is involved in modulating Tir-mediated pedestal formation. Surprisingly, EHEC mutant strain deficient in the E3 ligase activity induced more pedestals than the wild-type strain. The canonical EPEC strain E2348/69 normally lacks the nleL gene, and the ectopic expression of the wild-type EHEC nleL, but not the catalytically-deficient nleL(C753A) mutant, in this strain resulted in fewer actin-rich pedestals. Furthermore, we showed that the C. rodentium NleL homolog is a E3 ubiquitin ligase and is required for efficient infection of murine colonic epithelial cells in vivo. In summary, our study demonstrated that EHEC utilizes NleL E3 ubiquitin ligase activity to modulate Tir-mediated pedestal formation.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0019331
