Structure of the Cyclomodulin Cif from Pathogenic Escherichia coli

JOURNAL OF MOLECULAR BIOLOGY

卷:384

Article

Hsu, Yun²  Jubelin, Gregory¹  Taieb, Frederic¹  Nougayrede, Jean-Philippe¹  Oswald, Eric¹  Stebbins, C. Erec² 

[1] Ecole Natl Vet Toulouse, INRA, UMR1225, F-31076 Toulouse, France

[2] Rockefeller Univ, Lab Struct Microbiol, New York, NY 10021 USA

关键词: type III secretion;    virulence;    cell cycle;    Cif;    crystallography;   

DOI  :  10.1016/j.jmb.2008.09.051

来源: Elsevier

【 摘 要 】

Bacterial pathogens have evolved a sophisticated arsenal of virulence factors to modulate host cell biology. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) use a type III protein secretion system (T3SS) to inject microbial proteins into host cells. The T3SS effector cycle inhibiting factor (Cif) produced by EPEC and EHEC is able to block host eukaryotic cell-cycle progression. We present here a crystal structure of Cif, revealing it to be a divergent member of the superfamily of enzymes including cysteine proteases and acetyltransferases that share a common catalytic triad. Mutation of these conserved active site residues abolishes the ability of Of to block cell-cycle progression. Finally, we demonstrate that irreversible cysteine protease inhibitors do not abolish the Cif cytopathic effect, suggesting that another enzymatic activity may underlie the biological activity of this virulence factor. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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