Phosphorylation of major Porphyromonas gingivalis virulence factors is crucial for their processing and secretion

被引:11
作者
Nowakowska, Zuzanna [1 ]
Madej, Mariusz [1 ]
Grad, Sylwia [1 ]
Wang, Tiansong [2 ]
Hackett, Murray [2 ]
Miller, Daniel P. [3 ]
Lamont, Richard J. [4 ]
Potempa, Jan [1 ,4 ]
机构
[1] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Microbiol, Gronostajowa 7, PL-30387 Krakow, Poland
[2] Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA
[3] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, Richmond, VA 23298 USA
[4] Univ Louisville, Sch Dent, Dept Oral Immunol & Infect Dis, Louisville, KY 40292 USA
关键词
gingipains; phosphoproteome; phosphorylation; Porphyromonas gingivalis; virulence factors; PHOSPHOPEPTIDE ENRICHMENT; GINGIPAIN K; RAG LOCUS; PHOSPHOPROTEOME; MECHANISM; PROTEINS; KINASE; DOMAIN; RGPB; KGP;
D O I
10.1111/omi.12354
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
The main etiological agent of periodontitis is the anaerobic bacterium Porphyromonas gingivalis. Virulence of this pathogen is controlled by various mechanisms and executed by major virulence factors including the gingipain proteases, peptidylarginine deiminase (PPAD), and RagB, an outer membrane macromolecular transport component. Although the structures and functions of these proteins are well characterized, little is known about their posttranslational maturation. Here, we determined the phosphoproteome of P. gingivalis in which phosphorylated tyrosine residues constitute over 80% of all phosphoresidues. Multiple phosphotyrosines were found in gingipains, PPAD, and RagB. Although mutation of phosphorylated residues in PPAD and RagB had no effect on secretion or activity, site-directed mutagenesis showed that phosphorylation in hemagglutinin/adhesin domains of RgpA and Kgp, and in the catalytic domain of RgpB, had a strong influence on secretion, processing, and enzymatic activity. Moreover, preventing phosphorylation of one gingipain influenced the others, suggesting multiple phosphorylation-dependent pathways of gingipain maturation in P. gingivalis. Various candidate kinases including Ptk1 BY kinase and ubiquitous bacterial kinase 1 (UbK1) may be involved, but their contribution to gingipain processing and activation remains to be confirmed.
引用
收藏
页码:316 / 326
页数:11
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