Structural comparison and epitope analysis of outer-membrane protein PIA from strains of Neisseria gonorrhoeae with differing serovar specificities.
The sequences of the por genes, encoding outer-membrane protein PI, have been obtained from a number of strains of Neisseria gonorrhoeae that express PIA molecules with differing serovar specificities. The inferred amino acid sequences of the mature proteins each comprise 308 residues and show considerable homology, with the degree of sequence variation between PIA molecules being considerably less than seen previously with PIB, but more evenly distributed throughout the molecule. The positions of sequence variation are largely confined to the regions predicted to form one of eight surface-exposed loops, suggesting a more widespread distribution of potential antigenic diversity. The deduced amino acid sequences were used to synthesize peptides for epitope mapping experiments. Some epitopes responsible for serovar specificity or recognized by bactericidal monoclonal antibodies could be identified on the basis of their reactivity with simple linear peptides, whilst others recognized conformational epitopes. By comparison of sequence differences with mAb reactivity it was possible to identify regions that appear to contribute to such determinants, including separated regions of the molecule which together were required for the formation of the conformational epitopes. All the epitopes identified lie at or close to the apices of the predicted surface-exposed loops 1, 3, 6, or 8, focusing attention on these regions as accessible targets for immune attack.
Mee
B J
BJ
Molecular Microbiology Group, University of Southampton Medical School, Southampton General Hospital, UK.
Thomas
H
H
Cooke
S J
SJ
Lambden
P R
PR
Heckels
J E
JE
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D000939:Epitopes / Q000032:analysis / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics*; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000235:genetics*; D010449:Peptide Mapping; D018272:Porins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012703:Serotyping; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D000939:Epitopes; D018272:Porins; C057699:porin protein, Neisseria