title: Conserved structural mechanisms for autoinhibition in IpaH ubiquitin ligases.
abstract: The IpaH family of novel E3 ligase (NEL) enzymes occur in a variety of pathogenic and commensal bacteria that interact with eukaryotic hosts. We demonstrate that the leucine-rich repeat (LRR) substrate recognition domains of different IpaH enzymes autoinhibit the enzymatic activity of the adjacent catalytic novel E3 ligase domain by two distinct but conserved structural mechanisms. Autoinhibition is required for the in vivo biological activity of two IpaH enzymes in a eukaryotic model system. Autoinhibition was retro-engineered into a constitutively active IpaH enzyme from Yersinia pestis by introduction of single site substitutions, thereby demonstrating the conservation of autoregulatory infrastructure across the IpaH enzyme family.
authors: Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Yang-Chieh
authors: YC
authors: Chou
authors: Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Alexander F A
authors: AFA
authors: Keszei
authors: Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 1V7, Canada.
authors: John R
authors: JR
authors: Rohde
authors: Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada. Electronic address: md.tyers@umontreal.ca.
authors: Mike
authors: M
authors: Tyers
authors: Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Electronic address: sicheri@lunenfeld.ca.
authors: Frank
authors: F
authors: Sicheri
mesh_terms: D019943:Amino Acid Substitution; D017124:Conserved Sequence; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012763:Shigella flexneri / Q000201:enzymology; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015010:Yersinia pestis / Q000201:enzymology
chemical_list: D044767:Ubiquitin-Protein Ligases