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Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.

Jubelin G, Chavez CV, Taieb F, Banfield MJ, Samba-Louaka A, Nobe R, Nougayr├Ęde JP, Zumbihl R, Givaudan A, Escoubas JM, Oswald E - PLoS ONE (2009)

Bottom Line: The cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery.The X-ray crystal structure of Cif revealed it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases that share a conserved catalytic triad.Cif homologs from the enterobacteria Yersinia pseudotuberculosis, Photorhabdus luminescens, Photorhabdus asymbiotica and the beta-proteobacterium Burkholderia pseudomallei all induce cytopathic effects identical to those observed with Cif from pathogenic E. coli.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1225, Toulouse, France.

ABSTRACT
The cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery. Cif provokes cytopathic effects characterized by G(1) and G(2) cell cycle arrests, accumulation of the cyclin-dependent kinase inhibitors (CKIs) p21(waf1/cip1) and p27(kip1) and formation of actin stress fibres. The X-ray crystal structure of Cif revealed it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases that share a conserved catalytic triad. Here we report the discovery and characterization of four Cif homologs encoded by different pathogenic or symbiotic bacteria isolated from vertebrates or invertebrates. Cif homologs from the enterobacteria Yersinia pseudotuberculosis, Photorhabdus luminescens, Photorhabdus asymbiotica and the beta-proteobacterium Burkholderia pseudomallei all induce cytopathic effects identical to those observed with Cif from pathogenic E. coli. Although these Cif homologs are remarkably divergent in primary sequence, the catalytic triad is strictly conserved and was shown to be crucial for cell cycle arrest, cytoskeleton reorganization and CKIs accumulation. These results reveal that Cif proteins form a growing family of cyclomodulins in bacteria that interact with very distinct hosts including insects, nematodes and humans.

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The three residues of the CifEc catalytic triad are conserved among members of the Cif protein family.(A) ClustalW alignment between CifEc, CifYp, CifBp, CifPl, CifPa and GOS_5485515. Fully conserved residues are indicated by a red background and amino acids conserved more than 60 or 80% are indicated by a yellow or an orange background respectively. The cysteine, histidine and glutamine residues that form the catalytic triad of CifEc are indicated with blue stars. (B) Position of the fully conserved residues in the three dimensional structure of CifEc. Side chain carbon atoms of residues comprising the catalytic triad are coloured cyan. The remaining fully conserved residues cluster in three regions, as described in the text. Residues coloured yellow, including glycine positions indicated by spheres, are P107, G110, A113, N159, L163-G164, S186-G189, G191, D200-W201; in green are D170, D172, E264-D266; in purple are K118-L119 and N273.
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pone-0004855-g003: The three residues of the CifEc catalytic triad are conserved among members of the Cif protein family.(A) ClustalW alignment between CifEc, CifYp, CifBp, CifPl, CifPa and GOS_5485515. Fully conserved residues are indicated by a red background and amino acids conserved more than 60 or 80% are indicated by a yellow or an orange background respectively. The cysteine, histidine and glutamine residues that form the catalytic triad of CifEc are indicated with blue stars. (B) Position of the fully conserved residues in the three dimensional structure of CifEc. Side chain carbon atoms of residues comprising the catalytic triad are coloured cyan. The remaining fully conserved residues cluster in three regions, as described in the text. Residues coloured yellow, including glycine positions indicated by spheres, are P107, G110, A113, N159, L163-G164, S186-G189, G191, D200-W201; in green are D170, D172, E264-D266; in purple are K118-L119 and N273.

Mentions: A multiple alignment of the protein sequences (see Fig. 3A) was used to obtain the unrooted tree with Phylip's DrawTree software.


Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.

Jubelin G, Chavez CV, Taieb F, Banfield MJ, Samba-Louaka A, Nobe R, Nougayr├Ęde JP, Zumbihl R, Givaudan A, Escoubas JM, Oswald E - PLoS ONE (2009)

The three residues of the CifEc catalytic triad are conserved among members of the Cif protein family.(A) ClustalW alignment between CifEc, CifYp, CifBp, CifPl, CifPa and GOS_5485515. Fully conserved residues are indicated by a red background and amino acids conserved more than 60 or 80% are indicated by a yellow or an orange background respectively. The cysteine, histidine and glutamine residues that form the catalytic triad of CifEc are indicated with blue stars. (B) Position of the fully conserved residues in the three dimensional structure of CifEc. Side chain carbon atoms of residues comprising the catalytic triad are coloured cyan. The remaining fully conserved residues cluster in three regions, as described in the text. Residues coloured yellow, including glycine positions indicated by spheres, are P107, G110, A113, N159, L163-G164, S186-G189, G191, D200-W201; in green are D170, D172, E264-D266; in purple are K118-L119 and N273.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654923&req=5

pone-0004855-g003: The three residues of the CifEc catalytic triad are conserved among members of the Cif protein family.(A) ClustalW alignment between CifEc, CifYp, CifBp, CifPl, CifPa and GOS_5485515. Fully conserved residues are indicated by a red background and amino acids conserved more than 60 or 80% are indicated by a yellow or an orange background respectively. The cysteine, histidine and glutamine residues that form the catalytic triad of CifEc are indicated with blue stars. (B) Position of the fully conserved residues in the three dimensional structure of CifEc. Side chain carbon atoms of residues comprising the catalytic triad are coloured cyan. The remaining fully conserved residues cluster in three regions, as described in the text. Residues coloured yellow, including glycine positions indicated by spheres, are P107, G110, A113, N159, L163-G164, S186-G189, G191, D200-W201; in green are D170, D172, E264-D266; in purple are K118-L119 and N273.
Mentions: A multiple alignment of the protein sequences (see Fig. 3A) was used to obtain the unrooted tree with Phylip's DrawTree software.

Bottom Line: The cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery.The X-ray crystal structure of Cif revealed it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases that share a conserved catalytic triad.Cif homologs from the enterobacteria Yersinia pseudotuberculosis, Photorhabdus luminescens, Photorhabdus asymbiotica and the beta-proteobacterium Burkholderia pseudomallei all induce cytopathic effects identical to those observed with Cif from pathogenic E. coli.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1225, Toulouse, France.

ABSTRACT
The cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery. Cif provokes cytopathic effects characterized by G(1) and G(2) cell cycle arrests, accumulation of the cyclin-dependent kinase inhibitors (CKIs) p21(waf1/cip1) and p27(kip1) and formation of actin stress fibres. The X-ray crystal structure of Cif revealed it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases that share a conserved catalytic triad. Here we report the discovery and characterization of four Cif homologs encoded by different pathogenic or symbiotic bacteria isolated from vertebrates or invertebrates. Cif homologs from the enterobacteria Yersinia pseudotuberculosis, Photorhabdus luminescens, Photorhabdus asymbiotica and the beta-proteobacterium Burkholderia pseudomallei all induce cytopathic effects identical to those observed with Cif from pathogenic E. coli. Although these Cif homologs are remarkably divergent in primary sequence, the catalytic triad is strictly conserved and was shown to be crucial for cell cycle arrest, cytoskeleton reorganization and CKIs accumulation. These results reveal that Cif proteins form a growing family of cyclomodulins in bacteria that interact with very distinct hosts including insects, nematodes and humans.

Show MeSH
Related in: MedlinePlus