6GQ4

Neisseria gonorrhoeae Adhesin Complex Protein

6GQ4 の概要

• エントリーDOI: 10.2210/pdb6gq4/pdb
• 分子名称: Adhesin, SODIUM ION (3 entities in total)
• 機能のキーワード: neisseria gonorrhoeae-adhesin complex protein, ngo1981, bactericidal antibody, vaccine, immune system
• 由来する生物種: Neisseria gonorrhoeae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12416.07

構造登録者

Orr, C.M.,Tews, I. (登録日: 2018-06-07, 公開日: 2018-09-19, 最終更新日: 2024-10-23)

主引用文献

Almonacid-Mendoza, H.L.,Humbert, M.V.,Dijokaite, A.,Cleary, D.W.,Soo, Y.,Hung, M.C.,Orr, C.M.,Machelett, M.M.,Tews, I.,Christodoulides, M.
Structure of the RecombinantNeisseria gonorrhoeaeAdhesin Complex Protein (rNg-ACP) and Generation of Murine Antibodies with Bactericidal Activity against Gonococci.
mSphere, 3:-, 2018

PubMed Abstract: (gonococcus [Ng]) is the causative organism of the sexually transmitted disease gonorrhoea, and no effective vaccine exists currently. In this study, the structure, biological properties, and vaccine potential of the Ng-adhesin complex protein (Ng-ACP) are presented. The crystal structure of recombinant Ng-ACP (rNg-ACP) protein was solved at 1.65 Å. Diversity and conservation of Ng-ACP were examined in different species and gonococcal isolates (https://pubmlst.org/neisseria/ database) , and protein expression among 50 gonococcal strains in the Centers for Disease Control and Prevention/Food and Drug Administration (CDCP/FDA) AR Isolate Bank was examined by Western blotting. Murine antisera were raised to allele 10 (strain P9-17)-encoded rNg-ACP protein with different adjuvants and examined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and a human serum bactericidal assay. Rabbit antiserum to rNg-ACP was tested for its ability to prevent Ng-ACP from inhibiting human lysozyme activity Ng-ACP is structurally homologous to ACP and MliC/PliC lysozyme inhibitors. Gonococci expressed predominantly allele 10- and allele 6-encoded Ng-ACP (81% and 15% of isolates, respectively). Murine antisera were bactericidal (titers of 64 to 512,  < 0.05) for the homologous P9-17 strain and heterologous (allele 6) FA1090 strain. Rabbit anti-rNg-ACP serum prevented Ng-ACP from inhibiting human lysozyme with ∼100% efficiency. Ng-ACP protein was expressed by all 50 gonococcal isolates examined with minor differences in the relative levels of expression. rNg-ACP is a potential vaccine candidate that induces antibodies that (i) are bactericidal and (ii) prevent the gonococcus from inhibiting the lytic activity of an innate defense molecule. (gonococcus [Ng]) is the causative organism of the sexually transmitted disease gonorrhoea, and the organism is listed by the World Health Organization as a high-priority pathogen for research and development of new control measures, including vaccines. In this study, we demonstrated that the adhesin complex protein (Ng-ACP) was conserved and expressed by 50 gonococcal strains and that recombinant proteins induced antibodies in mice that killed the bacteria We determined the structure of Ng-ACP by X-ray crystallography and investigated structural conservation with ACP and MliC/PliC proteins from other bacteria which act as inhibitors of the human innate defense molecule lysozyme. These findings are important and suggest that Ng-ACP could provide a potential dual target for tackling gonococcal infections.

PubMed: 30305317
DOI: 10.1128/mSphere.00331-18

実験手法

X-RAY DIFFRACTION (1.65 Å)