Protein I: structure, function, and genetics

Abstract

The study of the major outer membrane (OM) protein, protein I (PI), of Neisseria gonorrhoeae has proven to be as fascinating, and as frustrating, as every other aspect of this remarkable bacterium. However, intensive studies over the last few years have provided significant insight into the structure, function, and genetics of this abundant, surfaceexposed porin protein. There are two forms of PI, which share up to 80% homology. The diversity of the exposed portion of the molecules among strains presents an everchanging immunogenic and antigenic dilemma to the reinfected host. Yet, it is the variability of the PI surface epitopes that has provided a precise method of serotyping N. gonorrhoeae, making it possible to monitor the prevalence and spread of strains within the host population and correlate functional differences between strains with PI structural types.Recent successes in cloning and sequencing of both P1 structural subclasses have already contributed to our understanding of the mechanisms) whereby N. gonorrhoeae generates PI structural diversity. Continued investigation is needed to clarify the relationship between PI type and disseminated disease, resistance to serum killing, auxotypic requirements, interaction with host cells, and resistance to antibiotics. Observations regarding the ability of PI to interact with eucaryotic membranes suggest a role for PI in the pathogenesis of N. gonorrhoeae, whereas immune responsiveness of patients to PI points to the possibility of a PI vaccine. Clearly, at the molecular level, PI represents all the mystery and intrigue that N. gonorrhoeae presents at the organism level. Certainly, much remains to be learned before we have a complete picture of the structure, function, and genetics of PI. STRUCTURE PI (73) is known to exist in two structurally related forms, designated subclass PIA and subclass PIB (61), which have different orientations in the OM (2, 4). A given strain or N. gonorrhoeae expresses a single, invariant PI of one of the other subclass, which accounts for up to 60% of the protein in the OM (36), whether grown aerobically or anaerobically (16). There is significant structural variation within the subclasses, resulting in proteins of different apparent molecular mass (52,72), different isoelectric points (with some as low as 5.5, but most close to 8.0) (3), and unique immunological reactivities (6,45,(61)(62)(63)75). PIAs tend to be smaller than PIBs, ranging in apparent molecular mass from about 34 to 36.5 kilodaltons (kDa), whereas PIBs range from about 36 to 38 kDa (38,52,72,73) (Fig. 1). Regardless of subclass, PIs appear to associate as trimeric porins which form hydrophilic channels through the OM (3,19,51,78). Proteins of both subclasses show immunological variation (6,45,(61)(62)(63)75), which tends to be localized in surface-exposed portions of the molecules (13,40,42,44,46,75 (13,14,23). There is 65 to 80% homology between PIA and amino acid sequences of the two PIBs, confirming similarities previously observed by peptide mapping (2,39,40,6...

Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein fromNeisseria meningitidisand the Binding of Factor H SCR 18 to 20 toNeisseria gonorrhoeaePorin

“…Meningococci with sialylated LOS that express gonococcal porin bind more fH than meningococci with sialylated LOS that express fHbp. Porin is the most abundant protein found in the outer membrane of gonococci (23,35). The amount of fHbp expressed varies among strains, but it is expressed at a much lower level than porin, even in strains that express high levels of fHbp (29).…”

Global Gene Expression and the Role of Sigma Factors in Neisseria gonorrhoeae in Interactions with Epithelial Cells

“…The incoming bacterium first binds to epithelial cells via interactions between specific receptors on the bacterial and host cell surfaces. The primary adhesins on the gonococcal cell surface are the type IV pili (77,78), although there are additional surface structures of the bacterium that can participate in adherence (18,22,33,37,46,47,67,82,84). Binding of gonococcal pili to host cells results in the induction of signal transduction pathways in the eukaryotic cell that affect multiple cellular processes (4,34,43,57,58,62).…”

RpoH Mediates the Expression of Some, but Not All, Genes Induced in Neisseria gonorrhoeae Adherent to Epithelial Cells

“…It is this feature that may account for our observations that cysK is necessary for gonococcal host cell interactions. The interaction between gonococci and host cells involves several proteinaceous structures on the surface of the bacterium, including pili (66), opacity proteins (43,71,73), and porins (31,36). Cysteine residues are highly conserved in the otherwise highly antigenically variable pilin, the major protein component of the gonococcal pilus (61), and are critical in the formation of disulfide bonds during assembly of the pilus fiber (50).…”