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PMID: 18997778 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases.

Nature structural & molecular biology ·Vol. 15 ·No. 12 ·2008-12-00 ·Pages 1293-301

Singer AU, Rohde JR, Lam R, Skarina T, Kagan O, Dileo R, Chirgadze NY, Cuff ME, Joachimiak A, Tyers M, Sansonetti PJ, Parsot C, Savchenko A

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-A 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.

MeSH Terms
Amino Acid Sequence Amino Acid Substitution Antigens, Bacterial/chemistry,genetics,metabolism Bacterial Proteins/chemistry,genetics,metabolism Conserved Sequence Crystallography, X-Ray Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Mutant Proteins/metabolism Mutation, Missense Protein Binding Protein Structure, Tertiary Sequence Alignment Ubiquitin-Protein Ligases/chemistry,genetics,metabolism
Chemicals
Antigens, Bacterial Bacterial Proteins Mutant Proteins ipaH protein, Shigella flexneri Ubiquitin-Protein Ligases
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Singer Alexander U
Ontario Centre for Structural Proteomics, Banting and Best Department for Medical Research, University of Toronto, C.H. Best Institute, Toronto, Ontario M5G1L5, Canada.
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
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1511
Published
2008-12-00
Epub
2008-00-09
Pages
1293-301
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC2764551
Subset
IM
Grants
NIGMS NIH HHS · P50 GM062414 · United States
NIGMS NIH HHS · U54 GM074942 · United States
NIGMS NIH HHS · U54 GM074942-04S2 · United States
NIGMS NIH HHS · GM62414-01 · United States
Databases
PDB
3CKD
External Links
PubMed source DOI: 10.1038/nsmb.1511 PMC Full Text View journal details
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