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- Title
Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases.
- Authors
Singer, Alexander U.; Rohde, John R.; Lam, Robert; Skarina, Tatiana; Kagan, Olga; DiLeo, Rosa; Chirgadze, Nickolay Y.; Cuff, Marianne E.; Joachimiak, Andrzej; Tyers, Mike; Sansonetti, Philippe J.; Parsot, Claude; Savchenko, Alexei
- Abstract
IpaH proteins are E3 ubiquitin ligases delivered by the type III secretion apparatus into host cells upon infection of humans by the Gram-negative pathogen Shigella flexneri. These proteins comprise a variable leucine-rich repeat–containing N-terminal domain and a conserved C-terminal domain harboring an invariant cysteine residue that is crucial for activity. IpaH homologs are encoded by diverse animal and plant pathogens. Here we demonstrate that the IpaH C-terminal domain carries the catalytic activity for ubiquitin transfer and that the N-terminal domain carries the substrate specificity. The structure of the IpaH C-terminal domain, determined to 2.65-Å resolution, represents an all-helical fold bearing no resemblance to previously defined E3 ubiquitin ligases. The conserved and essential cysteine residue lies on a flexible, surface-exposed loop surrounded by conserved acidic residues, two of which are crucial for IpaH activity.
- Subjects
PROTEIN analysis; LIGASES; SHIGELLA flexneri; UBIQUITIN; PATHOGENIC microorganisms; CYSTEINE proteinases
- Publication
Nature Structural & Molecular Biology, 2008, Vol 15, Issue 12, p1293
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.1511