A 3-dimensional trimeric ß-barrel model for Chlamydia MOMP contains conserved and novel elements of Gram-negative bacterial porins.

ABSTRACT

Chlamydia trachomatis is the most prevalent cause of bacterial sexually transmitted diseases and the leading cause of preventable blindness worldwide. Global control of Chlamydia will best be achieved with a vaccine, a primary target for which is the major outer membrane protein, MOMP, which comprises ~60% of the outer membrane protein mass of this bacterium. In the absence of experimental structural information on MOMP, three previously published topology models presumed a16-stranded barrel architecture. Here, we use the latest ß-barrel prediction algorithms, previous 2D topology modeling results, and comparative modeling methodology to build a 3D model based on the 16-stranded, trimeric assumption. We find that while a 3D MOMP model captures many structural hallmarks of a trimeric 16-stranded ß-barrel porin, and is consistent with most of the experimental evidence for MOMP, MOMP residues 320-334 cannot be modeled as ß-strands that span the entire membrane, as is consistently observed in published 16-stranded ß-barrel crystal structures. Given the ambiguous results for ß-strand delineation found in this study, recent publications of membrane ß-barrel structures breaking with the canonical rule for an even number of ß-strands, findings of ß-barrels with strand-exchanged oligomeric conformations, and alternate folds dependent upon the lifecycle of the bacterium, we suggest that although the MOMP porin structure incorporates canonical 16-stranded conformations, it may have novel oligomeric or dynamic structural changes accounting for the discrepancies observed.