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Peptide Sequence Region That is Essential for the Interactions of the Enterotoxigenic Bacteroides fragilis Metalloproteinase II with E-cadherin.


ABSTRACT: Bacteroides fragilis is a valuable anaerobic commensal and an essential component of the gut microbiome in humans. The presence of a short pathogenicity island in the genome is predominantly associated with the enterotoxigenic strains of B. fragilis. Metallopro-teinase II (MPII) and fragilysin (FRA) are the structurally related enzymes encoded by the pathogenicity island in the enterotoxigenic strains. Accordingly, there is a significant overlap between the cleavage preferences of MPII and FRA. These proteinases, however, are counter-transcribed in the bacterial genome suggesting their distinct and specialized functions in the course of infection. It is well established that FRA directly cleaves E-cadherin, a key protein of the cell-to-cell adhesion junctions in the intestinal epithelium. Counterintuitively, MPII directly binds to, rather than cleaves, E-cadherin. Structural modeling suggested that a potential E-cadherin binding site involves the C-terminal -helical region of the MPII catalytic domain. The sequence of this region is different in MPII and FRA. Here, we employed substitution mutagenesis of this C-terminal -helical region to isolate the MPII mutants with the potentially inactivated E-cadherin binding site. Overall, as a result of our modeling, mutagenesis and binding studies, we determined that the C-terminal ten residue segment is essential for the binding of MPII, but not of FRA3, to E-cadherin, and that the resulting MPII•E-cadherin complex does not impair E-cadherin-dependent cell-to-cell contacts. It is possible to envision that the putative cleavage targets of MPII should be explored not only on the host cell surface but also in B. fragilis.

SUBMITTER: Shiryaev SA 

PROVIDER: S-EPMC4425422 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Peptide Sequence Region That is Essential for the Interactions of the Enterotoxigenic Bacteroides fragilis Metalloproteinase II with E-cadherin.

Shiryaev Sergey A SA   Remacle Albert G AG   Cieplak Piotr P   Strongin Alex Y AY  

Journal of proteolysis 20141201 1


<i>Bacteroides fragilis</i> is a valuable anaerobic commensal and an essential component of the gut microbiome in humans. The presence of a short pathogenicity island in the genome is predominantly associated with the enterotoxigenic strains of B. <i>fragilis</i>. Metallopro-teinase II (MPII) and fragilysin (FRA) are the structurally related enzymes encoded by the pathogenicity island in the enterotoxigenic strains. Accordingly, there is a significant overlap between the cleavage preferences of  ...[more]

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