title: Involvement of Neisseria meningitidis lipoprotein GNA2091 in the assembly of a subset of outer membrane proteins.
abstract: GNA2091 of Neisseria meningitidis is a lipoprotein of unknown function that is included in the novel 4CMenB vaccine. Here, we investigated the biological function and the subcellular localization of the protein. We demonstrate that GNA2091 functions in the assembly of outer membrane proteins (OMPs) because its absence resulted in the accumulation of misassembled OMPs. Cell fractionation and protease accessibility experiments showed that the protein is localized at the periplasmic side of the outer membrane. Pulldown experiments revealed that it is not stably associated with the β-barrel assembly machinery, the previously identified complex for OMP assembly. Thus, GNA2091 constitutes a novel outer membrane-based lipoprotein required for OMP assembly. Furthermore, its location at the inner side of the outer membrane indicates that protective immunity elicited by this antigen cannot be due to bactericidal or opsonic activity of antibodies.
authors.affiliation: From the Department of Molecular Microbiology, Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands m.bos@uu.nl.
authors.forename: Martine P
authors.initials: MP
authors.lastname: Bos
authors.affiliation: From the Department of Molecular Microbiology, Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Grijpstra
authors.affiliation: From the Department of Molecular Microbiology, Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Ria
authors.initials: R
authors.lastname: Tommassen-van Boxtel
authors.affiliation: From the Department of Molecular Microbiology, Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Tommassen
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000378:metabolism*; D017124:Conserved Sequence; D017353:Gene Deletion; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D018272:Porins / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; D018272:Porins
keywords: BAM Complex; Bacteria; Membrane Biogenesis; Membrane Protein; Microbiology; Neisseria meningitidis; Vaccine; YraP
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11754-9
references.pmid: 16861298
references.citation: Nat Methods. 2008 Sep;5(9):781-7
references.pmid: 19160513
references.citation: Mol Microbiol. 2012 Jun;84(5):832-44
references.pmid: 22524202
references.citation: Mol Microbiol. 2004 Feb;51(4):1027-37
references.pmid: 14763978
references.citation: Cell. 2005 Apr 22;121(2):235-45
references.pmid: 15851030
references.citation: J Immunol. 2006 Jul 1;177(1):501-10
references.pmid: 16785547
references.citation: Science. 2003 Jan 10;299(5604):262-5
references.pmid: 12522254
references.citation: J Biol Chem. 2005 Oct 14;280(41):34409-19
references.pmid: 16079137
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1772-7
references.pmid: 19181847
references.citation: J Proteome Res. 2011 Apr 1;10(4):1848-59
references.pmid: 21210718
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10834-9
references.pmid: 16825336
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6400-5
references.pmid: 17404237
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5537-42
references.pmid: 18375759
references.citation: J Bacteriol. 2005 Jul;187(13):4552-61
references.pmid: 15968066
references.citation: J Biol Chem. 2004 Jun 25;279(26):27078-87
references.pmid: 15105427
references.citation: J Bacteriol. 2009 Nov;191(22):7074-85
references.pmid: 19767435
references.citation: Vaccine. 2009 Mar 4;27(10):1579-84
references.pmid: 19162117
references.citation: Cell Mol Life Sci. 2009 Sep;66(17):2789-804
references.pmid: 19399587
references.citation: J Biol Chem. 2011 Aug 19;286(33):28688-28696
references.pmid: 21705335
references.citation: J Bacteriol. 2007 Jan;189(1):244-53
references.pmid: 17056748
references.citation: Mol Microbiol. 2003 Nov;50(3):1017-30
references.pmid: 14617158
references.citation: Trends Biochem Sci. 2003 Jul;28(7):352-5
references.pmid: 12878000
references.citation: J Proteome Res. 2010 Jul 2;9(7):3730-40
references.pmid: 20521846
references.citation: EMBO J. 2004 Mar 24;23(6):1257-66
references.pmid: 15014442
references.citation: Res Microbiol. 2009 Nov;160(9):660-6
references.pmid: 19695325
references.citation: Science. 2000 Mar 10;287(5459):1809-15
references.pmid: 10710307
references.citation: Microbiology (Reading). 2010 Sep;156(Pt 9):2587-2596
references.pmid: 20616105
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9417-22
references.pmid: 15192148
references.citation: PLoS One. 2010 Jan 08;5(1):e8619
references.pmid: 20062535
references.citation: FEMS Microbiol Lett. 2009 May;294(2):216-24
references.pmid: 19374669
references.citation: J Biol Chem. 1999 Aug 27;274(35):24567-74
references.pmid: 10455120
references.citation: PLoS One. 2011;6(12):e29002
references.pmid: 22194974
references.citation: Vaccine. 2012 May 30;30 Suppl 2:B87-97
references.pmid: 22607904
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3487-91
references.pmid: 22331884
references.citation: Biochemistry. 2010 Apr 6;49(13):2768-77
references.pmid: 20199110
references.citation: Vaccine. 2010 Mar 11;28(12):2416-27
references.pmid: 20067752
references.citation: Cell Microbiol. 2002 Sep;4(9):599-611
references.pmid: 12390352
references.citation: J Bacteriol. 2011 Apr;193(7):1612-21
references.pmid: 21296967
references.citation: Annu Rev Microbiol. 2007;61:191-214
references.pmid: 17506684