The fic domain: regulation of cell signaling by adenylylation.
Mol Cell
; 34(1): 93-103, 2009 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-19362538
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Transdução de Sinais
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Pasteurellaceae
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Fatores de Virulência
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Antígenos de Bactérias
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article