Does the Importance of the C-Terminal Residues in the Maturation of RgpB from
            <i>Porphyromonas gingivalis</i>
            Reveal a Novel Mechanism for Protein Export in a Subgroup of Gram-Negative Bacteria?

Nguyen, Ky-Anh; Travis, James; Potempa, Jan

doi:10.1128/jb.01530-06

Cited by 110 publications

(199 citation statements)

References 59 publications

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“…Our recent publications confirm and extend these results (213,214,215). Most of the LPS-like glycan moieties appear to occur at the C-terminus of the polypeptide chain and seem to serve to anchor the gingipain molecule into the outer membrane (146,178,188). There is also diversity and variable levels of carbohydrate modifications demonstrated in the various isoforms of the catalytic domains of Rgp (41,60).…”

Section: Gingipain Glycosylationsupporting

confidence: 70%

“…Consistent with this hypothesis is the recent observation that truncation of the last two residues (valyl-lysine) from the C terminus of RgpB is sufficient to create an inactive version of the protein that lacks the post-translational glycosylation seen in the wild type, and the protein remains trapped behind the outer membrane. Alanine scanning of the last five residues also revealed the importance of the C-terminal motif in mediating correct post-translational modification of the protein (146). RgpB is required for the normal post-translational glycosylation of Arggingipains derived from rgpA (165).…”

Section: Gingipain Glycosylationmentioning

confidence: 99%

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Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

Sheets

Robles-Price²,

McKenzie³

et al. 2008

Front Biosci

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Porphyromonas gingivalis, a major periodontal pathogen, must acquire nutrients from host derived substrates, overcome oxidative stress and subvert the immune system. These activities can be coordinated via the gingipains which represent the most significant virulence factor produced by this organism. In the context of our contribution to this field, we will review the current understanding of gingipain biogenesis, glycosylation, and regulation, as well as discuss their role in oxidative stress resistance and apoptosis. We can postulate a model, in which gingipains may be part of the mechanism for P. gingivalis virulence. KeywordsPorphyromonas gingivalis; gingipains; apoptosis; caspase-independent apoptosis; oxidative stress; VimA; anoikis; N-cadherin; VE-cadherin; integrin β1; VimA; VimE; VimF; DNA repair; glycosylation; virulence; host cell survival; HRgpA; RgpB; Kgp; Review INTRODUCTIONP. gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiological agent of periodontal disease and is also linked to cardiovascular disease and other systemic diseases [reviewed in (43,103)]. The inflammatory nature of periodontal disease implies that innate host defense mechanisms play a vital role in limiting bacterial growth. During active infection including tissue invasion, toxic reactive oxygen metabolites (e.g. superoxides, hydrogen peroxide and hydroxyl radicals) are mostly generated by polymorphonuclear leukocytes and macrophages (27,29). In order to survive in the inflammatory environment of the periodontal pocket, the bacterium must not only obtain nutrients for growth, but also overcome oxidative stress and subvert the immune defense system. Coordinated regulation of these activities would be beneficial to the bacterium. While there is documented evidence of the response of P. gingivalis to environmental stimulus (56,117,126), one possible mechanism for coordination may occur via the gingipains produced by this bacterium. The presence of P. gingivalis in the periodontal pocket and the high levels of gingipain activity detected in gingival crevicular fluid could implicate a role for gingipains in the destruction of the highly vascular periodontal tissue. Protease-associated degradation of cell-cell adhesion proteins on epithelial and endothelial cells resulting in cell death will compromise tissue integrity and facilitate spreading of the bacterium. Furthermore, degradation of the immune response components will facilitate the survival of the organism. Together, these activities may also satisfy the nutritional requirements of the organism. Gingipain-dependent heme accumulation on the bacterium cell surface may also act as an "oxidative sink", thus, leading to protection against oxidative stress (191,193). We will discuss the role of the gingipains in the survival/pathogenicity of P. gingivalis and the unique vim (virulence modulating) locus that is involved in regulation of the gingipains. We will highlight some of our observations that are consistent with the hypothesis that the gingipain...

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Section: Gingipain Glycosylationsupporting

confidence: 70%

Section: Gingipain Glycosylationmentioning

confidence: 99%

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

Sheets

Robles-Price²,

McKenzie³

et al. 2008

Front Biosci

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show abstract

“…were calculated from 4 independent measurements. Subcellular Fractionations-All procedures were carried out at 4°C or on ice according to a previously reported method (27), with slight modifications. Briefly, a 20-ml culture of P. gingivalis KDP136, a gingipain-null mutant (28), in the log-phase was centrifuged at 6,000 ϫ g for 15 min.…”

Section: Construction Of P Gingivalis Strains With Disrupted Dppmentioning

confidence: 99%

Identification and Characterization of Prokaryotic Dipeptidyl-peptidase 5 from Porphyromonas gingivalis

Ohara‐Nemoto

Rouf

Naito

et al. 2014

Journal of Biological Chemistry

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Background: Dipeptidyl-peptidases (DPPs) are key factors for amino acid metabolism and bacterial growth of asaccharolytic Porphyromonas gingivalis. Results: DPP5, which is specific for Ala and hydrophobic residues, is expressed in the periplasmic space of P. gingivalis. Conclusion: DPP5 was discovered in prokaryotes for the first time. Significance: The discovery of DPP5 expands understanding of amino acid and energy metabolism in prokaryotes.

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“…Chromosomal integration of the mutated regions into the P. gingivalis genome was achieved via double homologous recombination as described previously (49). Briefly, 1 g of purified plasmid DNA was electroporated into P. gingivalis strain W83 competent cells (2.5 kV, 4 ms; Bio-Rad Micropulser).…”

Section: Generation Of P Gingivalis Mutant Strains-strains Incorporamentioning

confidence: 99%

Structural insights unravel the zymogenic mechanism of the virulence factor gingipain K from Porphyromonas gingivalis, a causative agent of gum disease from the human oral microbiome

Pomowski

Usón

Nowakowska

et al. 2017

Journal of Biological Chemistry

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Edited by Joseph JezSkewing of the human oral microbiome causes dysbiosis and preponderance of bacteria such as Porphyromonas gingivalis, the main etiological agent of periodontitis. P. gingivalis secretes proteolytic gingipains (Kgp and RgpA/B) as zymogens inhibited by a pro-domain that is removed during extracellular activation. Unraveling the molecular mechanism of Kgp zymogenicity is essential to design inhibitors blocking its activity. Here, we found that the isolated 209-residue Kgp pro-domain is a boomerang-shaped all-␤ protein similar to the RgpB pro-domain. Using composite structural information of Kgp and RgpB, we derived a plausible homology model and mechanism of Kgpregulating zymogenicity. Accordingly, the pro-domain would laterally attach to the catalytic moiety in Kgp and block the active site through an exposed inhibitory loop. This loop features a lysine (Lys 129 ) likely occupying the S 1 specificity pocket and exerting latency. Lys 129 mutation to glutamate or arginine led to misfolded protein that was degraded in vivo. Mutation to alanine gave milder effects but still strongly diminished proteolytic activity, without affecting the subcellular location of the enzyme. Accordingly, the interactions of Lys 129 within the S 1 pocket are also essential for correct folding. Uniquely for gingipains, the isolated Kgp pro-domain dimerized through an interface, which partially overlapped with that between the catalytic moiety and the pro-domain within the zymogen, i.e. both complexes are mutually exclusive. Thus, pro-domain dimerization, together with partial rearrangement of the active site upon activation, explains the lack of inhibition of the pro-domain in trans. Our results reveal that the specific latency mechanism of Kgp differs from those of Rgps.

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Does the Importance of the C-Terminal Residues in the Maturation of RgpB from Porphyromonas gingivalis Reveal a Novel Mechanism for Protein Export in a Subgroup of Gram-Negative Bacteria?

Cited by 110 publications

References 59 publications

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

Identification and Characterization of Prokaryotic Dipeptidyl-peptidase 5 from Porphyromonas gingivalis

Structural insights unravel the zymogenic mechanism of the virulence factor gingipain K from Porphyromonas gingivalis, a causative agent of gum disease from the human oral microbiome

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