Fic domain catalyzed adenylylation: Insight provided by the structural analysis of the type IV secretion system effector BepA

Palanivelu, D. V. and Goepfert, A. and Meury, M. and Guye, P. and Dehio, C. and Schirmer, T.. (2011) Fic domain catalyzed adenylylation: Insight provided by the structural analysis of the type IV secretion system effector BepA. Protein Science, 20 (3). pp. 492-499.

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Official URL: http://edoc.unibas.ch/dok/A5844157

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Numerous bacterial pathogens subvert cellular functions of eukaryotic host cells by the injection of effector proteins via dedicated secretion systems. The type IV secretion system (T4SS) effector protein BepA from Bartonella henselae is composed of an N-terminal Fic domain and a C-terminal BID domain, the latter being responsible for T4SS-mediated translocation into host cells. A proteolysis resistant fragment (residues 10 to 302) that includes the Fic domain shows auto-adenylylation activity and adenylyl transfer onto Hela cell extract proteins as demonstrated by autoradiography upon incubation with alpha-[(32)P]-ATP. Its crystal structure, determined to 2.9 A resolution by the SeMet-SAD method, exhibits the canonical Fic fold including the HPFxxGNGRxxR signature motif with several elaborations in loop regions and an additional beta-rich domain at the C-terminus. Upon crystal soaking with ATP/Mg(2+), additional electron density indicated the presence of a PP(i)/Mg(2+) moiety, the side product of the adenylylation reaction, in the anion binding nest of the signature motif. Based on this information and that of the recent structure of IbpA(Fic2) in complex with the eukaryotic target protein Cdc42, we present a detailed model for the ternary complex of Fic with the two substrates, ATP/Mg(2+) and target tyrosine. The model is consistent with an in-line nucleophilic attack of the deprotonated side-chain hydroxyl group onto the alpha-phosphorus of the nucleotide to accomplish AMP transfer. Furthermore, a general, sequence independent mechanism of target positioning through antiparallel beta-strand interactions between enzyme and target is suggested.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
UniBasel Contributors:Dehio, Christoph and Goepfert, Arnaud and Schirmer, Tilman
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cambridge University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Nov 2017 10:31
Deposited On:14 Sep 2012 06:38

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