Involvement of Neisseria meningitidis lipoprotein GNA2091 in the assembly of a subset of outer membrane proteins

J Biol Chem. 2014 May 30;289(22):15602-10. doi: 10.1074/jbc.M113.539510. Epub 2014 Apr 22.

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.

Keywords: BAM Complex; Bacteria; Membrane Biogenesis; Membrane Protein; Microbiology; Neisseria meningitidis; Vaccine; YraP.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Vaccines / metabolism*
  • Conserved Sequence
  • Gene Deletion
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Molecular Sequence Data
  • Mutagenesis
  • Neisseria meningitidis, Serogroup B / genetics
  • Neisseria meningitidis, Serogroup B / metabolism*
  • Phenotype
  • Porins / metabolism
  • Protein Structure, Tertiary

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Lipoproteins
  • Porins