PMID- 25713028 OWN - NLM STAT- MEDLINE DCOM- 20150824 LR - 20191210 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 29 IP - 6 DP - 2015 Jun TI - Neisseria meningitis GNA1030 is a ubiquinone-8 binding protein. PG - 2260-7 LID - 10.1096/fj.14-263954 [doi] AB - 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). CI - (c) FASEB. FAU - Donnarumma, Danilo AU - Donnarumma D AD - Novartis Vaccines, Siena, Italy. FAU - Golfieri, Giacomo AU - Golfieri G AD - Novartis Vaccines, Siena, Italy. FAU - Brier, Sebastien AU - Brier S AD - Novartis Vaccines, Siena, Italy. FAU - Castagnini, Marta AU - Castagnini M AD - Novartis Vaccines, Siena, Italy. FAU - Veggi, Daniele AU - Veggi D AD - Novartis Vaccines, Siena, Italy. FAU - Bottomley, Matthew James AU - Bottomley MJ AD - Novartis Vaccines, Siena, Italy. FAU - Delany, Isabel AU - Delany I AD - Novartis Vaccines, Siena, Italy. FAU - Norais, Nathalie AU - Norais N AD - Novartis Vaccines, Siena, Italy nathalie.norais@novartis.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150220 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (4CMenB vaccine) RN - 0 (Anti-Bacterial Agents) RN - 0 (Antigens, Bacterial) RN - 0 (Bacterial Proteins) RN - 0 (Disulfides) RN - 0 (Meningococcal Vaccines) RN - 0 (Methacrylates) RN - 0 (Oxidants) RN - 0 (Periplasmic Proteins) RN - 0 (Thiazoles) RN - 1339-63-5 (Ubiquinone) RN - 642-15-9 (Antimycin A) RN - 6VY98BQ7NB (myxothiazol) RN - BBX060AN9V (Hydrogen Peroxide) RN - CQA993F7P8 (ubiquinone 8) RN - EC 7.1.1.8 (Electron Transport Complex III) SB - IM MH - Amino Acid Sequence MH - Anti-Bacterial Agents/pharmacology MH - Antigens, Bacterial/chemistry/genetics/*metabolism MH - Antimycin A/pharmacology MH - Bacterial Proteins/chemistry/genetics/*metabolism MH - Blotting, Western MH - Cell Survival/drug effects/genetics MH - Cloning, Molecular MH - Disulfides/metabolism MH - Electron Transport Complex III/antagonists & inhibitors/metabolism MH - Hydrogen Peroxide/pharmacology MH - Mass Spectrometry/methods MH - Meningococcal Vaccines/metabolism MH - Methacrylates/pharmacology MH - Molecular Sequence Data MH - Mutation MH - Neisseria meningitidis/genetics/growth & development/*metabolism MH - Oxidants/pharmacology MH - Periplasmic Proteins/chemistry/genetics/metabolism MH - Protein Binding MH - Protein Multimerization MH - Thiazoles/pharmacology MH - Ubiquinone/*metabolism OTO - NOTNLM OT - Bexsero vaccine OT - NUbp OT - native mass spectrometry EDAT- 2015/02/26 06:00 MHDA- 2015/08/25 06:00 CRDT- 2015/02/26 06:00 PHST- 2014/10/21 00:00 [received] PHST- 2015/01/20 00:00 [accepted] PHST- 2015/02/26 06:00 [entrez] PHST- 2015/02/26 06:00 [pubmed] PHST- 2015/08/25 06:00 [medline] AID - fj.14-263954 [pii] AID - 10.1096/fj.14-263954 [doi] PST - ppublish SO - FASEB J. 2015 Jun;29(6):2260-7. doi: 10.1096/fj.14-263954. Epub 2015 Feb 20.