Structural and functional diversity of metalloproteinases encoded by the Bacteroides fragilis pathogenicity island. (22nd April 2014)

• Record Type: Journal Article
• Authors: Shiryaev, Sergey A.; Aleshin, Alexander E.; Muranaka, Norihito; Kukreja, Muskan; Routenberg, David A.; Remacle, Albert G.; Liddington, Robert C.; Cieplak, Piotr; Kozlov, Igor A.; Strongin, Alex Y.
• Is Part Of: FEBS journal. Volume 281:Number 11(2014)
• Page Start: 2487
• Page End: 2502
• Publication Date: 2014-04-22
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.12804
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs12804-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>Bacteroides fragilis</italic> causes the majority of anaerobic infections in humans. The presence of a pathogenicity island in the genome discriminates pathogenic and commensal <italic>B. fragilis</italic> strains. The island encodes metalloproteinase II (MPII), a potential virulence protein, and one of three homologous fragilysin isozymes (FRA; also termed <italic>B. fragilis</italic> toxin or BFT). Here, we report biochemical data on the structural–functional characteristics of the <italic>B. fragilis</italic> pathogenicity island proteases by reporting the crystal structure of MPII at 2.13 Å resolution, combined with detailed characterization of the cleavage preferences of MPII and FRA3 (as a representative of the FRA isoforms), identified using a high‐throughput peptide cleavage assay with 18 583 substrate peptides. We suggest that the evolution of the MPII catalytic domain can be traced to human and archaebacterial proteinases, whereas the prodomain fold is a feature specific to MPII and FRA. We conclude that the catalytic domain of both MPII and FRA3 evolved differently relative to the prodomain, and that the prodomain evolved specifically to fit the <italic>B. fragilis</italic> pathogenicity. Overall, our data provide insights into the evolution of cleavage specificity and activation mechanisms in the virulent metalloproteinases.</p> </abstract>