title: Neisseria meningitis GNA1030 is a ubiquinone-8 binding protein.
abstract: Bexsero, a new vaccine against Neisseria meningitidis serogroup B (MenB), is composed of 3 main recombinant proteins and an outer membrane vesicle component. One of the main bactericidal antigens, neisseria heparin binding antigen (NHBA), is present as a fusion protein with the accessory protein genome-derived neisserial antigen (GNA) 1030 to further increase its immunogenicity. The gene encoding for GNA1030 is present and highly conserved in all Neisseria strains, and although orthologs are present in numerous species, its biologic function is unknown. Native mass spectrometry was used to demonstrate that GNA1030 forms a homodimer associated with 2 molecules of ubiquinone-8 (Ub8), a cofactor mainly involved in the electron transport chain and with antioxidant properties. Disc diffusion assays on the wild-type and knockout mutant of GNA1030, in the presence of various compounds, suggested that GNA1030 is not involved in oxidative stress or electron chain transport per se, although it contributes to constitutive refilling of the inner membrane with Ub8. These studies shed light on an accessory protein present in Bexsero and reveal functional insights into the family of related proteins. On the basis of our findings, we propose to name the protein neisseria ubiquinone binding protein (NUbp).
authors.affiliation: Novartis Vaccines, Siena, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Donnarumma
authors.affiliation: Novartis Vaccines, Siena, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Golfieri
authors.affiliation: Novartis Vaccines, Siena, Italy.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Brier
authors.affiliation: Novartis Vaccines, Siena, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Castagnini
authors.affiliation: Novartis Vaccines, Siena, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Veggi
authors.affiliation: Novartis Vaccines, Siena, Italy.
authors.forename: Matthew James
authors.initials: MJ
authors.lastname: Bottomley
authors.affiliation: Novartis Vaccines, Siena, Italy.
authors.forename: Isabel
authors.initials: I
authors.lastname: Delany
authors.affiliation: Novartis Vaccines, Siena, Italy nathalie.norais@novartis.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Norais
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000968:Antimycin A / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003001:Cloning, Molecular; D004220:Disulfides / Q000378:metabolism; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D013058:Mass Spectrometry / Q000379:methods; D022401:Meningococcal Vaccines / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D033903:Periplasmic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D013844:Thiazoles / Q000494:pharmacology; D014451:Ubiquinone / Q000378:metabolism*
chemical_list: C570015:4CMenB vaccine; D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004220:Disulfides; D022401:Meningococcal Vaccines; D008689:Methacrylates; D016877:Oxidants; D033903:Periplasmic Proteins; D013844:Thiazoles; D014451:Ubiquinone; D000968:Antimycin A; C030517:myxothiazol; D006861:Hydrogen Peroxide; C030778:ubiquinone 8; D014450:Electron Transport Complex III
keywords: Bexsero vaccine; NUbp; native mass spectrometry