TheTreponema denticolaDgcA protein (TDE0125) is a functional diguanylate cyclase
| Autor: | Richard T. Marconi, Edward J A Schuler, Dhara T Patel, Nathaniel S. O'Bier |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
GTP' Microbiology Dystrophin-associated glycoprotein complex 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Protein Domains Guanosine monophosphate Humans Immunology and Allergy Cyclic GMP Gene Periodontal Diseases Phylogeny 030304 developmental biology 0303 health sciences Treponema General Immunology and Microbiology biology 030306 microbiology Chemistry Escherichia coli Proteins Treponema denticola Gene Expression Regulation Bacterial Sequence Analysis DNA General Medicine biology.organism_classification Recombinant Proteins stomatognathic diseases Open reading frame Infectious Diseases Mutagenesis Site-Directed biology.protein Diguanylate cyclase Guanosine Triphosphate Phosphorus-Oxygen Lyases |
| Zdroj: | Pathogens and Disease. 79 |
| ISSN: | 2049-632X |
| Popis: | Periodontal disease (PD) is a progressive inflammatory condition characterized by degradation of the gingival epithelium, periodontal ligament, and alveolar bone ultimately resulting in tooth loss. Treponema denticola is a keystone periopathogen that contributes to immune dysregulation and direct tissue destruction. As periodontal disease develops, T. denticola must adapt to environmental, immunological and physiochemical changes in the subgingival crevice. Treponema denticola produces bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP), an important regulatory nucleotide. While T. denticola encodes several putative diguanylate cyclases (DGCs), none have been studied and hence the biological role of c-di-GMP in oral treponemes remains largely unexplored. Here, we demonstrate that the T. denticola open reading frame, TDE0125, encodes a functional DGC designated as DgcA (Diguanylate cyclase A). The dgcA gene is universal among T. denticola isolates, highly conserved and is a stand-alone GGEEF protein with a GAF domain. Recombinant DgcA converts GTP to c-di-GMP using either manganese or magnesium under aerobic and anaerobic reaction conditions. Size exclusion chromatography revealed that DgcA exists as a homodimer and in larger oligomers. Site-directed mutagenesis of residues that define the putative inhibitory site of DgcA suggest that c-di-GMP production is allosterically regulated. This report is the first to characterize a DGC of an oral treponeme. |
| Databáze: | OpenAIRE |
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