The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a Spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The OmpA domain is an eight-stranded membrane-spanning beta-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work we describe the identification of four novel OmpA-like beta-barrels from Borrelia afzelii, the most common cause of erythema migrans rash in Europe. Structural characterisation of one these proteins (BAPKO0422) by small angle X-ray scattering (SAXS) and circular dichroism indicate a compact globular structure rich in beta-strand consistent with a monomeric beta-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO0422 adopts a peanut shape with dimensions 25 x 45 rA. Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal Phe residue commonly found in Proteobacterial OM proteins is replaced by Ile/Leu or Asn. BAPKO0422 is demonstrated to bind human factor-H and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value.
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- Department of Biological and Geographical Sciences - Subject Leader Biomedicine/Pharmacology
- School of Applied Sciences
- Cellular and Molecular Models of Disease Centre - Member
- Biopolymer Research Centre - Member
- Microbial Therapeutics and Infection Control Centre - Associate Member