G09SecL04Tpc2: Difference between revisions
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Since NMR chemical shifts are greatly sensitive to magnetic (local) environments, they are great for sensing conformational changes; NMR chemical-shift perturbation was an important method in identifying this three- loop epitope of OspA, but more importantly it also portrayed that these three loops were strongly antigenic. In a study conducted in 2000, Wei Ding and fellow colleagues illustrated the <scene name='G09SecL04Tpc2/Ospala2/2'>binding site</scene> through NMR and crystallography: LA-2 makes a concave-like groove over the 3 loops on the tip of the c-terminus through direct contact by heavy and light chains includng interactions between its R groups. | Since NMR chemical shifts are greatly sensitive to magnetic (local) environments, they are great for sensing conformational changes; NMR chemical-shift perturbation was an important method in identifying this three- loop epitope of OspA, but more importantly it also portrayed that these three loops were strongly antigenic. In a study conducted in 2000, Wei Ding and fellow colleagues illustrated the <scene name='G09SecL04Tpc2/Ospala2/2'>binding site</scene> through NMR and crystallography: LA-2 makes a concave-like groove over the 3 loops on the tip of the c-terminus through direct contact by heavy and light chains includng interactions between its R groups. | ||
Subsequent NMR results suggested that the overall c-terminal was basically unchanged by LA-2 binding, except for the minor shifts in the conformations of the 3 loops; the conformations results in order to accommodate interactions | Subsequent NMR results suggested that the overall c-terminal was basically unchanged by LA-2 binding, except for the minor shifts in the conformations of the 3 loops; the conformations results in order to accommodate interactions with the Fab. Further analysis of amide proton exchange rates supported this by proving that the n-terminal and central sheet domains were stable while the c-terminal domain illustrated great fluctuation in respect to its 3 loops. Specifically, Loops 2 and 3 were only subject to slight change in comparison to Loop 1’s dramatic increase. | ||
Loop 1 protrudes the most along the C-terminal barrel domain probably because it has extra amino acid residues. More importantly, since it has a greater degree of protrusion, it has greater surface exposure making it particularly antigenic. Further evidence through Western blotting methods suggests that Loop 1 plays the greatest role in allowing LA-recognition of OspA. | Loop 1 protrudes the most along the C-terminal barrel domain probably because it has extra amino acid residues. More importantly, since it has a greater degree of protrusion, it has greater surface exposure making it particularly antigenic. Further evidence through Western blotting methods suggests that Loop 1 plays the greatest role in allowing LA-recognition of OspA. | ||
By understanding the binding | By understanding the binding site between OspA’s three loops and LA-2, greater research has been done in vaccinations against OspA. It is important to note that the vaccination is virtually ineffective once transmission into the host is complete mainly due to OspA’s down-regulation and hiding maneuvers. LA-2 antibody is a major proponent for effectiveness of the current OspA vaccine, but its effectiveness depends on different strains of borrelia. LA-2 recognizes the epitope of OspA from B.burgdorferi, but does recognize European strains including B.afzellii and B.garinii. This is due to sequence variation. Alanine208 and Alanine215 are great examples where this amino acid residue differs from afzellii and garinii species. <scene name='G09SecL04Tpc2/Ospala2/3'>Ala208 Zoom</scene> | ||
==Pathogenesis of Lyme Neuroborreliosis (LNB)== | ==Pathogenesis of Lyme Neuroborreliosis (LNB)== | ||
