Involvement of Neisseria Meningitidis Lipoprotein GNA2091 in the Assembly of a Subset of Outer Membrane Proteins

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2014 Apr 24

PMID 24755216

Citations 17

Authors

Martine P Bos

Jan Grijpstra

Ria Tommassen-van Boxtel

Jan Tommassen

Affiliations

Soon will be listed here.

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.

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References

Wu T, McCandlish A, Gronenberg L, Chng S, Silhavy T, Kahne D . Identification of a protein complex that assembles lipopolysaccharide in the outer membrane of Escherichia coli. Proc Natl Acad Sci U S A. 2006; 103(31):11754-9. PMC: 1544242. DOI: 10.1073/pnas.0604744103. View

Typas A, Nichols R, Siegele D, Shales M, Collins S, Lim B . High-throughput, quantitative analyses of genetic interactions in E. coli. Nat Methods. 2009; 5(9):781-7. PMC: 2700713. DOI: 10.1038/nmeth.1240. View

Anwari K, Webb C, Poggio S, Perry A, Belousoff M, Celik N . The evolution of new lipoprotein subunits of the bacterial outer membrane BAM complex. Mol Microbiol. 2012; 84(5):832-44. PMC: 3359395. DOI: 10.1111/j.1365-2958.2012.08059.x. View

Grizot S, Buchanan S . Structure of the OmpA-like domain of RmpM from Neisseria meningitidis. Mol Microbiol. 2004; 51(4):1027-37. DOI: 10.1111/j.1365-2958.2003.03903.x. View

Wu T, Malinverni J, Ruiz N, Kim S, Silhavy T, Kahne D . Identification of a multicomponent complex required for outer membrane biogenesis in Escherichia coli. Cell. 2005; 121(2):235-45. DOI: 10.1016/j.cell.2005.02.015. View

Madico G, Welsch J, Lewis L, McNaughton A, Perlman D, Costello C . The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. J Immunol. 2006; 177(1):501-10. PMC: 2248442. DOI: 10.4049/jimmunol.177.1.501. View

Voulhoux R, Bos M, Geurtsen J, Mols M, Tommassen J . Role of a highly conserved bacterial protein in outer membrane protein assembly. Science. 2003; 299(5604):262-5. DOI: 10.1126/science.1078973. View

Stenberg F, Chovanec P, Maslen S, Robinson C, Ilag L, von Heijne G . Protein complexes of the Escherichia coli cell envelope. J Biol Chem. 2005; 280(41):34409-19. DOI: 10.1074/jbc.M506479200. View

Walton T, Sandoval C, Fowler C, Pardi A, Sousa M . The cavity-chaperone Skp protects its substrate from aggregation but allows independent folding of substrate domains. Proc Natl Acad Sci U S A. 2009; 106(6):1772-7. PMC: 2644113. DOI: 10.1073/pnas.0809275106. View

10.

Maddalo G, Stenberg-Bruzell F, Gotzke H, Toddo S, Bjorkholm P, Eriksson H . Systematic analysis of native membrane protein complexes in Escherichia coli. J Proteome Res. 2011; 10(4):1848-59. DOI: 10.1021/pr101105c. View

11.

Giuliani M, Adu-Bobie J, Comanducci M, Arico B, Savino S, Santini L . A universal vaccine for serogroup B meningococcus. Proc Natl Acad Sci U S A. 2006; 103(29):10834-9. PMC: 2047628. DOI: 10.1073/pnas.0603940103. View

12.

Sklar J, Wu T, Gronenberg L, Malinverni J, Kahne D, Silhavy T . Lipoprotein SmpA is a component of the YaeT complex that assembles outer membrane proteins in Escherichia coli. Proc Natl Acad Sci U S A. 2007; 104(15):6400-5. PMC: 1851043. DOI: 10.1073/pnas.0701579104. View

13.

Ruiz N, Gronenberg L, Kahne D, Silhavy T . Identification of two inner-membrane proteins required for the transport of lipopolysaccharide to the outer membrane of Escherichia coli. Proc Natl Acad Sci U S A. 2008; 105(14):5537-42. PMC: 2291135. DOI: 10.1073/pnas.0801196105. View

14.

Onufryk C, Crouch M, Fang F, Gross C . Characterization of six lipoproteins in the sigmaE regulon. J Bacteriol. 2005; 187(13):4552-61. PMC: 1151791. DOI: 10.1128/JB.187.13.4552-4561.2005. View

15.

Tinsley C, Voulhoux R, Beretti J, Tommassen J, Nassif X . Three homologues, including two membrane-bound proteins, of the disulfide oxidoreductase DsbA in Neisseria meningitidis: effects on bacterial growth and biogenesis of functional type IV pili. J Biol Chem. 2004; 279(26):27078-87. DOI: 10.1074/jbc.M313404200. View

16.

Volokhina E, Beckers F, Tommassen J, Bos M . The beta-barrel outer membrane protein assembly complex of Neisseria meningitidis. J Bacteriol. 2009; 191(22):7074-85. PMC: 2772484. DOI: 10.1128/JB.00737-09. View

17.

Jacobsson S, Thulin Hedberg S, Molling P, Unemo M, Comanducci M, Rappuoli R . Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease. Vaccine. 2009; 27(10):1579-84. DOI: 10.1016/j.vaccine.2008.12.052. View

18.

Walther D, Rapaport D, Tommassen J . Biogenesis of beta-barrel membrane proteins in bacteria and eukaryotes: evolutionary conservation and divergence. Cell Mol Life Sci. 2009; 66(17):2789-804. PMC: 2724633. DOI: 10.1007/s00018-009-0029-z. View

19.

Bos M, Tommassen J . The LptD chaperone LptE is not directly involved in lipopolysaccharide transport in Neisseria meningitidis. J Biol Chem. 2011; 286(33):28688-28696. PMC: 3190676. DOI: 10.1074/jbc.M111.239673. View

20.

Sperandeo P, Cescutti R, Villa R, di Benedetto C, Candia D, Deho G . Characterization of lptA and lptB, two essential genes implicated in lipopolysaccharide transport to the outer membrane of Escherichia coli. J Bacteriol. 2006; 189(1):244-53. PMC: 1797204. DOI: 10.1128/JB.01126-06. View