Protein I: structure, function, and genetics.

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, surface-exposed 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 ever-changing immunogenic and antigenic dilemma to the rein-fected 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 immuno-logical reactivities (6, 45, 61-63, 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 PIs also interact …