6GQ4
Neisseria gonorrhoeae Adhesin Complex Protein
Summary for 6GQ4
| Entry DOI | 10.2210/pdb6gq4/pdb |
| Descriptor | Adhesin, SODIUM ION (3 entities in total) |
| Functional Keywords | neisseria gonorrhoeae-adhesin complex protein, ngo1981, bactericidal antibody, vaccine, immune system |
| Biological source | Neisseria gonorrhoeae |
| Total number of polymer chains | 1 |
| Total formula weight | 12416.07 |
| Authors | |
| Primary citation | 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 Cited by 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: 30305317DOI: 10.1128/mSphere.00331-18 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
Download full validation report
