G04SecL04Tpc1: Difference between revisions

Another surface protein of note in the B. Burgdorferi is OspA, which is 53% similar to OspB. This is due to some structural similarities in the proteins. Also, the change in conformation of OspA after binding to the LA2 antibody is very similar to that of OspB when binding with H6831. The H6831 and LA2 antibodies are also structurally similar and both are bind at C-terminal of the particular surface protein (Becker et al. 2005).  

OspA has a structure composed of a single alpha helix and 21 anti-parallel beta strands.  OspA also contains a B-cell epitope that binds with LA-2 Fab, an antigen combining fragment of the LA-2 monoclonal antibody, which is a major component in effective OspA vaccinations (Ding et al. 2000). Early vaccination for OspA is critical as OspA is only up-regulated during late stages of the disease; anti-OspA antibodies can only kill spirochetes in the tick gut, but is ineffective once it has migrated into host (Rupprecht et al. 2008). Through NMR chemical shift-perturbation and crystallographic identification, the LA-2 antibody is shown to make direct contact with the three loops in the C-terminal tip, which consists of approximately 39 amino acid residues (Ding et al. 2000). Specifically, the LA-2 Fab makes a concave groove over the three loops using all six of its light and heavy variable chain domains seen by NMR-perturbation analysis (Ding et al. 2000). The sequence variation of Loop 1 (~17 residues) has even shown to dominate LA-2 recognition of the OspA antigen; furthermore, position 208 (Residue Alanine) is a major dynamic for current studies of antibody cross-reactivity between different strains of the Borrelia that transmit Lyme disease (Ding et al 2000).