Molecular cell, 2009-04, Vol.34 (1), p.93-103
2009
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- Autor(en) / Beteiligte
- Titel
- The Fic Domain: Regulation of Cell Signaling by Adenylylation
- Ist Teil von
- Molecular cell, 2009-04, Vol.34 (1), p.93-103
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2009
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- We show that the secreted antigen, IbpA, of the respiratory pathogen Histophilus somni induces cytotoxicity in mammalian cells via its Fic domains. Fic domains are defined by a core HPFxxGNGR motif and are conserved from bacteria to humans. We demonstrate that the Fic domains of IbpA catalyze a unique reversible adenylylation event that uses ATP to add an adenosine monophosphate (AMP) moiety to a conserved tyrosine residue in the switch I region of Rho GTPases. This modification requires the conserved histidine of the Fic core motif and renders Rho GTPases inactive. We further demonstrate that the only human protein containing a Fic domain, huntingtin yeast-interacting protein E (HYPE), also adenylylates Rho GTPases in vitro. Thus, we classify Fic domain-containing proteins as a class of enzymes that mediate bacterial pathogenesis as well as a previously unrecognized eukaryotic posttranslational modification that may regulate key signaling events.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2009.03.008Titel-ID: cdi_proquest_miscellaneous_67131474
- Format
- –
- Schlagworte
- Actin Cytoskeleton - metabolism, Adenosine Monophosphate - metabolism, Adenosine Triphosphate - metabolism, Amino Acid Motifs, Antigens, Bacterial - chemistry, Antigens, Bacterial - physiology, Bacterial Proteins - chemistry, Bacterial Proteins - physiology, Carrier Proteins - chemistry, Carrier Proteins - metabolism, Carrier Proteins - physiology, CELLBIO, Cysteine Endopeptidases - chemistry, HeLa Cells, Histidine - chemistry, Histidine - metabolism, Humans, Membrane Proteins - chemistry, Membrane Proteins - metabolism, Membrane Proteins - physiology, MICROBIO, Molecular Sequence Data, Nucleotidyltransferases, Pasteurellaceae - immunology, Pasteurellaceae - pathogenicity, Phosphoric Diester Hydrolases - pharmacology, PROTEINS, rac GTP-Binding Proteins - metabolism, rho GTP-Binding Proteins - chemistry, rho GTP-Binding Proteins - metabolism, Sequence Alignment, Signal Transduction, Substrate Specificity, Tyrosine - metabolism, Virulence Factors - chemistry, Virulence Factors - physiology