Outer envelope proteins: PorB

A predicted protein CT713 with weak sequence homology (20.4%) to the major outer membrane protein (ompA) and a molecular weight of 37 KDa was identified in the whole genomic sequence of C. trachomatis [Stephens et al., 1998] and C. pneumoniae [Shirai et al., 2000]. Residues 138 - 157 and 162 - 180 also have a cation-dependent mannose 6 phosphate signature [See: Los Alamos database]. The protein is expressed at low level in the chlamydial outer membrane complex throughout the developmental cycle and, importantly, it is surface exposed. This protein, variously termed PorB or ompB, was virtually identical in C. trachomatis serovars D, B, C and L2. However there was only 59.3% identity between PorB of C. trachomatis and Chlamydophila pneumoniae [Kubo & Stephens, 2000; Stephens & Lammell, 2000].

PorB and MOMP are both porins, facilitating the diffusion of solutes through the outer membrane. However, PorB has different pore-forming activity to MOMP. MOMP is a general porin, permitting the diffusion of a wide variety of compounds, notably glucose and glutamate. These are transported across the inner membrane by UhpC and GltT respectively [Stephens et al., 1998]. In contrast, PorB is present in much lower amounts in the outer envelope which, together with the observation that it is ineffective as a general transporter of polysaccharides and amino acid solutes, suggests that it must have a more specific role. However PorB efficiently transports dicarboxylic acids such as 2-oxoglutarate which chlamydiae require because they have an incomplete tricarboxylic acid cycle, lacking citrate synthase, aconitase and isocitrate dehydrogenase. Thus, PorB probably serves to get dicarboxylic acids across the outer membrane while SodTi, a dicarboxylate transporter orthologue similar to a transporter of 2-oxoglutarate into spinach chloroplasts, translocates dicarboxylate across the inner membrane to the stroma in exchange for malate [Kubo & Stephens, 2001]. It has been shown that chlamydiae can use 2-oxoglutarate as an external carbon source to support their replication [Iliffe-Lee & McClarty, 2000].

Antibody to PorB has been identified in human sera [Sanchez-Campillo et al., 1999]. PorB is a surface exposed protein and antibody to it has neutralizing activity. Synthetic peptides have been used to locate the epitopes responsible for generating neutralizing antibody. Four major antigenic clusters corresponding to Phe(34)-Leu(59) (B1-2 and B1-3), Asp(112) -Glu(145) (B2-3 and B2-4), Gly(179)-Ala(225) (B3-2 to B3-4), and Val(261)-Asn(305) (B4-4 to B5-2) were identified. Peptide-specific antisera raised to these surface-accessible Ags neutralized chlamydial infectivity and cross reacted with analogous C. pneumoniae peptides. Immunoaccessible PorB Ags may be useful for chlamydial vaccine development, particular as PorB shows less serovar variability than MOMP [Kawa & Stephens, 2002].

[MEW comment: PorB may be a useful additional component of a potential chlamydial vaccine along with other candidate outer membrane proteins [Stephens & Lammell, 2000]. However, as for MOMP, relatively large amounts of antibody are required for neutralization. The fundamental problem remains; how to sustain sufficient levels of neutralizing antibody at epithelial surfaces.]

NEXT: Antigens_Proteomics.CysteineRichProteinsof the chlamydial outer membrane complex

References

Iliffe-Lee, E. R. & McClarty, G. (2000). Regulation of carbon metabolism in Chlamydia trachomatis. Molecular Microbiology 38, 20 - 30.

Kawa, D. E. & Stephens, R. S. (2002). Antigenic topology of chlamydial PorB protein and identification of targets for immune neutralization of infectivity. Journal of Immunology 168, 5184 - 5191. Full article [Acrobat]

Kubo, A. & Stephens, R. S. (2000). Characterization and functional analysis of PorB, a Chlamydia porin and neutralizing target. Molecular Microbiology 38, 772 - 780.

Kubo, A. & Stephens, R. S. (2001). Substrate-specific diffusion of select dicarboxylates through Chlamydia trachomatis PorB. Microbiology 147, 3135 - 3140. Full article [Acrobat]

Sanchez-Campillo, M., Bini, L., Comanducci, M., Raggiaschi, R., Marzocchi, B., Pallini, V. & Ratti, G. (1999). Identification of immunoreactive proteins of Chlamydia trachomatis by Western blot analysis of a two-dimensional electrophoresis map with patient sera. Electrophoresis 20, 2269 - 2279.

Stephens, R. S., Kalman, S., Lammel, C. et al., (1998). Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754 - 759. +

Stephens, R. S. & Lammel, C. J. (2001). Chlamydia outer membrane protein discovery using genomics. Current Opinion in Microbiology 4, 16 - 20. [Review]. Full article* [Acrobat]

Topic revision: r4 - 2010-08-10 - MeWard
 
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