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Envelope proteins

Macrophage infectivity potentiator (MIP)

MIP is a 27 kDa membrane protein located in both elementary and reticulate bodies and first described by  [Lundemose et al., 1991] who noted its homology with the macrophage infectivity potentiator (mip) gene of Legionella pneumophila.  The entire gene from C. trachomatis serovar L2 was sequenced [Lundemose et al., 1992] and found to be highly conserved within C. trachomatis. Despite its membrane location, no surface exposed epitopes were detected by immunofluorescence or immuno electron microscopy although a complement plus antibody -dependent decrease in infectivity for tissue culture cells was noted. [Comment: It is unclear, but unlikely that MIP is surface exposed.]. The C-terminal region of the protein, like that of  Legionella   MIP, showed strong homology with eukaryotic and prokaryotic binding proteins for the immunosuppressive drug FK506 [Lundemose et al., 1992]. FK506 is a natural peptido-macrolide containing an acylated pipecolic acid residue [Rahfeld et al., 1996]. The FK506 binding proteins [reviewed by Galat, 2000; sequence characteristics given by Trandinh et al., 1992] to which chlamydial MIP is homologous are peptidyl-prolyl cis-trans isomerases (PPIases). [Note: These are but one of three different kinds of PPIases, the other two being the cyclophilins, which bind cyclosporin A and the parvulins; some bacteria including E. coli have all three kinds]. 

For all prokaryotic MIP-like proteins, the predicted structure of the N terminal part of the proteins contains up to three larger -helices followed by a short -sheet or turn. No trans-membrane spanning region could be found by estimation of free transfer energies of the appropriate -helical structures [Rahfeld et al., 1996]. However in C. trachomatis a signal peptidase II recognition sequence was deduced from the open reading frame and palmitic acid was incorporated into the native protein, indicating a membrane, probably periplasmic localization of the protein [Lundemose et al., 1992]. The natural translated protein has been identified in two dimensional gels [Sanchez-Campillo et al., 1999]. 

C. psittaci MIP was sequenced in 1996 and shown to be surrounded by three genes encoding asparagine tRNA ligase (AspS), rRNA methylase (SpoU), and thioredoxin (TrxA) [Rockey et al., 1996]. This arrangement was subsequently confirmed by the various chlamydial genome sequences. Recombinant chlamydial MIP-like protein exhibits PPIase activity and is characteristically inhibited by either rapamycin or FK506 [Lundemose et al., 1993]. These inhibitors at 25 micromolar also have a modest effect on chlamydial infectivity for McCoy cells in tissue culture, suggesting MIP  may play a role in chlamydial entry. 

The PPIases act to assist the refolding of proteins and their transfer across the periplasmic space [Rahfeld et al., 1996]. In Legionella they are superficially located and are thought to assist intracellular survival in macrophages, although they are found in both virulent and avirulent organisms.

[Comment: these proteins have been somewhat neglected since 1996, though their importance to chlamydiae is still not fully understood].

[MEW] November 2002

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References

Galat, A. (2000). Sequence diversification of the FK506-binding proteins in several different genomes. European Journal of Biochemistry 267, 4945 - 4959 Full article [Interesting paper but Chlamydiales were not among the chosen genomes]

Lundemose, A. G., Birkelund, S., Fey, S. J., Larsen, P. M. & Christiansen, G. (1991). Chlamydia trachomatis contains a protein similar to the Legionella pneumophila mip gene product. Molecular Microbiology 5, 109 - 115.

Lundemose, A. G., Rouch, D. A., Birkelund, S., Christiansen, G. & Pearce, J. H. (1992). Chlamydia trachomatis Mip-like protein. Molecular Microbiology 6, 2539 - 2548.

Lundemose, A. G., Kay, J. E.  Pearce, J. H. (1993) Chlamydia trachomatis Mip-like protein has peptidyl-prolyl cis/trans isomerase activity that is inhibited by FK506 and rapamycin and is implicated in initiation of chlamydial infection. Molecular Microbiology 7, 777 - 783.

Rahfeld, J. U., Rucknagel, K. P., Stoller, G., Horne, S. M., Schierhorn, A., Young, K. D. & Fischer, G. (1996). Isolation and amino acid sequence of a new 22-kDa FKBP-like peptidyl-prolyl cis/trans-isomerase of Escherichia coli. Similarity to Mip-like proteins of pathogenic bacteria. Journal of Biological Chemistry 271, 22130 - 22138. Full article   Sequence alignment [Excellent study of FKBPs in prokaryotes generally, including a sequence alignment with C. trachomatis, Coxiella etc]

Rockey, D. D., Chesebro, B. B., Heinzen, R. A. & Hackstadt, T. (1996). A 28 kDa major immunogen of Chlamydia psittaci shares identity with Mip proteins of Legionella spp. and Chlamydia trachomatis - cloning and characterization of the C. psittaci mip-like gene. Microbiology 142, 945 - 953.

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.

Trandinh, C. C., Pao, G. M. & Saier, M. H. Jr. (1992). Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl-prolyl cis-trans isomerases. FASEB Journal 6, 3410 - 3420,

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