title: Structural and evolutionary inference from molecular variation in Neisseria porins.
abstract: The porin proteins of the pathogenic Neisseria species, Neisseria gonorrhoeae and Neisseria meningitidis, are important as serotyping antigens, putative vaccine components, and for their proposed role in the intracellular colonization of humans. A three-dimensional structural homology model for Neisseria porins was generated from Escherichia coli porin structures and N. meningitidis PorA and PorB sequences. The Neisseria sequences were readily assembled into the 16-strand beta-barrel fold characteristic of porins, despite relatively low sequence identity with the Escherichia proteins. The model provided information on the spatial relationships of variable regions of peptide sequences in the PorA and PorB trimers and insights relevant to the use of these proteins in vaccines. The nucleotide sequences of the porin genes from a number of other Neisseria species were obtained by PCR direct sequencing and from GenBank. Alignment and analysis of all available Neisseria porin sequences by use of the structurally conserved regions derived from the PorA and PorB structural models resulted in the recovery of an improved phylogenetic signal. Phylogenetic analyses were consistent with an important role for horizontal genetic exchange in the emergence of different porin classes and confirmed the close evolutionary relationships of the porins from N. meningitidis, N. gonorrhoeae, Neisseria lactamica, and Neisseria polysaccharea. Only members of this group contained three conserved lysine residues which form a potential GTP binding site implicated in pathogenesis. The model placed these residues on the inside of the pore, in close proximity, consistent with their role in regulating pore function when inserted into host cells.
authors.affiliation: Department of Biomolecular Sciences, UMIST, Manchester M60 1QD, United Kingdom.
authors.forename: J P
authors.initials: JP
authors.lastname: Derrick
authors.forename: R
authors.initials: R
authors.lastname: Urwin
authors.forename: J
authors.initials: J
authors.lastname: Suker
authors.forename: I M
authors.initials: IM
authors.lastname: Feavers
authors.forename: M C
authors.initials: MC
authors.lastname: Maiden
mesh_terms: D000595:Amino Acid Sequence; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009343:Neisseria / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D009344:Neisseria gonorrhoeae / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D009345:Neisseria meningitidis / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010802:Phylogeny; D018272:Porins / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D000942:Antigens, Bacterial; D017931:DNA Primers; D018272:Porins