1.B.6 The OmpA-OmpF Porin (OOP) Family
The large OOP family includes the functionally well characterized OmpA porin of E. coli as well as the OmpF (OprF) porin of Pseudomonas aeruginosa (Baldermann et al., 1998). Both proteins contain an N-terminal 8 β-strand transmembrane domain and a cell surface C-terminal peptidoglycan-interaction domain (Grizot and Buchanan, 2004). Only this latter domain exhibits extensive sequence similarity with E. coli OmpA and M. tuberculosis OmpATb. OmpATb has been reported to be a low activity channel that is essential for adaptation of M. tuberculosis to low pH and survival in mouse macrophage, but channel activity has been questioned (Niederweis, 2003).OmpA proteins and their many homologues probably all form structures consisting of eight transmembrane, all next neighbor, antiparallel, amphipathic β-strands. They form small β-barrels with short turns at the periplasmic barrel ends, and long flexible loops at the external ends. A 1.65 Å resolution monomeric structure is available for the E. coli OmpA porin (Pautsch and Schulz, 2000). A tetrameric quarternary structure has been proposed in which the subunits of the tetramer dissociate relatively readily. However, monomeric structures are proposed for other members of this family (Gribun et al., 2004).
The OmpA family consists of heat-modifiable, surface-exposed, porin proteins that are in high-copy number in the outer membranes of many Gram-negative bacteria. OmpA proteins generally have an N-terminal, eight-stranded, anti-parallel β barrel embedded in the outer membrane while the C-terminal domain is globular and located in the periplasmic space. Escherichia coli OmpA is the best characterized of the proteins, but homologues from pathogenic bacteria include Pseudomonas aeruginosa OprF, Haemophilus influenzae P5, Klebsiella pneumoniae OmpA, and Chlamydia trachomatis major outer membrane protein (MOMP). OmpA from the veterinary pathogens Mannheimia haemolytica, Haemophilus parasuis, Leptospira interrogans, and Pasteurella multocida have been studied to a lesser extent (Confer and Ayalew 2013). Among many of the pathogenic bacteria, OmpA proteins have important pathogenic roles including bacterial adhesion, invasion, or intracellular survival as well as evasion of host defenses or stimulators of pro-inflammatory cytokine production. These pathogenic roles are most commonly associated with central nervous system, respiratory and urogenital diseases. Additionally, OmpA family proteins can serve as targets of the immune system with immunogenicity related to surface-exposed loops of the molecule. In several cases, OmpA proteins are under evaluation as potential vaccine candidates (Confer and Ayalew 2013).
The P. aeruginosa OmpF (1.B.6.1.2) exists in two conformations: a minority single domain conformer and a majority two domain conformer (Sugawara et al., 2006). Only the former inserts into liposomes to give high conductance channel activity (Nestorovich et al., 2006). The active conformation is present only for short times (Nestorovich et al., 2006) accounting for low permeability reported previously.
The OOP family proteins may exhibit structural similarity with well-characterized virulence proteins such as the neisserial opacity (Opa) adhesins, the Salmonella Rck complement resistance protein, the Salmonella PagC intramacrophage survival protein, and the Yersinia Ail attachment/invasion protein (Baldermann et al., 1998). However, sequence similarity with these proteins is insufficient to establish homology. These protein β-barrels resemble those of the lipocalin family although the members of these two protein families serve entirely different functions and show no observable sequence similarity. OmpA of E. coli is required for bacterial conjugation and for maintenance of outer membrane stability.
Members of the Ail/Lom family of outer membrane proteins, which are homologous to OmpA of E. coli (1.B.6.1.2), provide protection from complement-dependent killing for a number of pathogenic bacteria. The Y. pestis KIM genome encodes four Ail/Lom family proteins. The Ail (Attachment inversion locus; 182aas) protein is essential for Y. pestis to resist complement-mediated killing. High-level expression of the three other Y. pestis Ail/Lom family proteins (the y1682, y2034, and y2446 proteins) provided no protection against complement-mediated bacterial killing (Bartra et al., 2008).
Intragenic duplication of the 8-stranded OmpX β-barrel produces a functional pore (Omp2X) the size of the OmpC porin (1.B.1.1.3) channel, a natural 16 stranded β-barrel (Arnold et al. 2007). This provides a potential mechanism for generating larger porins of 16 TMSs from smaller porins of 8 TMSs.