28
views
0
recommends
+1 Recommend
2 collections
    0
    shares

      The APC waiver has been extended to also apply to manuscripts submitted until March 31, 2024.

      To submit to the journal, please click here.

      • Record: found
      • Abstract: found
      • Article: found

      Gingipains from Porphyromonas gingivalis - Complex domain structures confer diverse functions.

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Gingipains, a group of arginine or lysine specific cysteine proteinases (also known as RgpA, RgpB and Kgp), have been recognized as major virulence factors in Porphyromonas gingivalis. This bacterium is one of a handful of pathogens that cause chronic periodontitis. Gingipains are involved in adherence to and colonization of epithelial cells, haemagglutination and haemolysis of erythrocytes, disruption and manipulation of the inflammatory response, and the degradation of host proteins and tissues. RgpA and Kgp are multi-domain proteins composed of catalytic domains and haemagglutinin/adhesin (HA) regions. The structure of the HA regions have previously been defined by a gingipain domain structure hypothesis which is a set of putative domain boundaries derived from the sequences of fragments of these proteins extracted from the cell surface. However, multiple sequence alignments and hidden Markov models predict an alternative domain architecture for the HA regions of gingipains. In this alternate model, two or three repeats of the so-called "cleaved adhesin" domains (and one other undefined domain in some strains) are the modules which constitute the substructure of the HA regions. Recombinant forms of these putative cleaved adhesin domains are indeed stable folded protein modules and recently determined crystal structures support the hypothesis of a modular organisation of the HA region. Based on the observed K2 and K3 structures as well as multiple sequence alignments, it is proposed that all the cleaved adhesin domains in gingipains will share the same β-sandwich jelly roll fold. The new domain model of the structure for gingipains and the haemagglutinin (HagA) proteins of P. gingivalis will guide future functional studies of these virulence factors.

          Related collections

          Most cited references106

          • Record: found
          • Abstract: found
          • Article: not found

          Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis.

          Periodontal disease is common among adults in the US and is a potential source of chronic inflammation. Recent data have suggested an important role for chronic inflammation in the development of coronary heart disease (CHD). To aid the United States Preventive Services Task Force (USPSTF) in evaluating whether periodontal disease is an independent novel risk factor for incident CHD. Studies were identified by searching Medline (1966 through March 2008) and reviewing prior systematic reviews, reference lists, and consulting experts. Prospective cohort studies that assessed periodontal disease, Framingham risk factors, and coronary heart disease incidence in the general adult population without known CHD were reviewed and quality rated using criteria developed by the USPSTF. Meta-analysis of good and fair quality studies was conducted to determine summary estimates of the risk of CHD events associated with various categories of periodontal disease. We identified seven articles of good or fair quality from seven cohorts. Several studies found periodontal disease to be independently associated with increased risk of CHD. Summary relative risk estimates for different categories of periodontal disease (including periodontitis, tooth loss, gingivitis, and bone loss) ranged from 1.24 (95% CI 1.01-1.51) to 1.34 (95% CI 1.10-1.63). Risk estimates were similar in subgroup analyses by gender, outcome, study quality, and method of periodontal disease assessment. Periodontal disease is a risk factor or marker for CHD that is independent of traditional CHD risk factors, including socioeconomic status. Further research in this important area of public health is warranted.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis.

            Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent in the initiation and progression of severe forms of periodontal disease. An opportunistic pathogen, P. gingivalis can also exist in commensal harmony with the host, with disease episodes ensuing from a shift in the ecological balance within the complex periodontal microenvironment. Colonization of the subgingival region is facilitated by the ability to adhere to available substrates such as adsorbed salivary molecules, matrix proteins, epithelial cells, and bacteria that are already established as a biofilm on tooth and epithelial surfaces. Binding to all of these substrates may be mediated by various regions of P. gingivalis fimbrillin, the structural subunit of the major fimbriae. P. gingivalis is an asaccharolytic organism, with a requirement for hemin (as a source of iron) and peptides for growth. At least three hemagglutinins and five proteinases are produced to satisfy these requirements. The hemagglutinin and proteinase genes contain extensive regions of highly conserved sequences, with posttranslational processing of proteinase gene products contributing to the formation of multimeric surface protein-adhesin complexes. Many of the virulence properties of P. gingivalis appear to be consequent to its adaptations to obtain hemin and peptides. Thus, hemagglutinins participate in adherence interactions with host cells, while proteinases contribute to inactivation of the effector molecules of the immune response and to tissue destruction. In addition to direct assault on the periodontal tissues, P. gingivalis can modulate eucaryotic cell signal transduction pathways, directing its uptake by gingival epithelial cells. Within this privileged site, P. gingivalis can replicate and impinge upon components of the innate host defense. Although a variety of surface molecules stimulate production of cytokines and other participants in the immune response, P. gingivalis may also undertake a stealth role whereby pivotal immune mediators are selectively inactivated. In keeping with its strict metabolic requirements, regulation of gene expression in P. gingivalis can be controlled at the transcriptional level. Finally, although periodontal disease is localized to the tissues surrounding the tooth, evidence is accumulating that infection with P. gingivalis may predispose to more serious systemic conditions such as cardiovascular disease and to delivery of preterm infants.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Inflammation and Alzheimer's disease: possible role of periodontal diseases.

              The molecular and cellular mechanisms responsible for the etiology and pathogenesis of Alzheimer's disease (AD) have not been defined; however, inflammation within the brain is thought to play a pivotal role. Studies suggest that peripheral infection/inflammation might affect the inflammatory state of the central nervous system. Chronic periodontitis is a prevalent peripheral infection that is associated with gram-negative anaerobic bacteria and the elevation of serum inflammatory markers including C-reactive protein. Recently, chronic periodontitis has been associated with several systemic diseases including AD. In this article we review the pathogenesis of chronic periodontitis and the role of inflammation in AD. In addition, we propose several potential mechanisms through which chronic periodontitis can possibly contribute to the clinical onset and progression of AD. Because chronic periodontitis is a treatable infection, it might be a readily modifiable risk factor for AD.
                Bookmark

                Author and article information

                Journal
                Eur J Microbiol Immunol (Bp)
                European journal of microbiology & immunology
                Akademiai Kiado Zrt.
                2062-509X
                2062-509X
                Mar 2011
                : 1
                : 1
                Affiliations
                [1 ] School of Molecular Bioscience, University of Sydney NSW Australia.
                Article
                EuJMI_1(2011)1/7
                10.1556/EuJMI.1.2011.1.7
                3894813
                24466435
                a776faa7-30e3-45ba-98bc-9b8c765f6a7f
                History

                gingipain,haemagglutinin,lysine- and arginine-specific cysteine proteases,Porphyromonas gingivalis,cleaved adhesin

                Comments

                Comment on this article