The K1K2 region of Lys-gingipain of Porphyromonas gingivalis blocks induction of HLA expression by gamma interferon.
In the context of periodontal disease, cysteine proteinases or gingipains from Porphyromonas gingivalis have been implicated in the hydrolysis of cytokines, including gamma interferon (IFN-γ). This cytokine plays a crucial role in host defenses, in part, by regulating expression of major histocompatibility complex molecules. Our recent analysis has identified three structurally defined modules, K1, K2, and K3, of the hemagglutinin region of the lysine gingipain Kgp. These three structurally homologous domains have a common β-sandwich topology that is similar to that found in a superfamily of adhesins and carbohydrate binding domains. The three Kgp hemagglutinin modules are distinguished by variation in some of the loops projecting from the β-sandwich core. Recombinant products corresponding to both single and multidomain regions as well as native Kgp bound IFN-γ with similar affinities. Among the adhesin domain constructs, only the K1K2 polypeptide inhibited the upregulation of HLA-1 expression in a human erythroleukemia (K562) line induced by both recombinant and native IFN-γ. The K1K2 polypeptide also inhibited HLA-DR expression induced by IFN-γ in human umbilical vein endothelial cells. These effects were competitively inhibited by coincubation with sodium or potassium chloride solution. The N-terminal residues of IFN-γ were implicated in mediating the effect of K1K2, while antibody binding to loop 1 of K2 blocked the action of K1K2. The findings indicate the potential significance of structurally defined Kgp adhesin modules in the inactivation of IFN-γ but also the potential of K1K2 in locating the target for the catalytic domain of Kgp.
Institute of Dental Research, Westmead Millennium Institute and Centre for Oral Health, Westmead Hospital, Sydney, New South Wales, Australia. plwyun@gmail.com
Peter L
PL
Yun
Nan
N
Li
Charles A
CA
Collyer
Neil
N
Hunter
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D000080867:Gingipain Cysteine Endopeptidases; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D020014:K562 Cells; D008958:Models, Molecular; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits; D011994:Recombinant Proteins; D013997:Time Factors
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D006680:HLA Antigens; C116124:K1K2 peptide; D010455:Peptides; D011994:Recombinant Proteins; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases