OspA L03 Group2: Difference between revisions

First recognized in 1957, [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] has been estimated to affect between 20 and 100 cases per 100,000 individuals in the United States <ref name=Ruprecht >PMID: 18097481</ref>. The peak infection rates of this disease occur approximately between the months of May and August in North America <ref name=Onrust>PMID: 10730551</ref>. The causative agent for this disease is a bacterial vector of [http://www.ucmp.berkeley.edu/bacteria/spirochetes.html spirochetes], called [http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borrelia burgdorferi], which were found in the gut of the [http://en.wikipedia.org/wiki/Ixodes Ixodes] tick. The bacteria spread through the bite of the tick forming severe skin lesions. Other health complications include chronic [http://en.wikipedia.org/wiki/Arthritis arthritis], and neurologic and cardiac abnormalities <ref name=Burgdorferi>PMID: 7043737</ref>. From 10-12 weeks of infestation, other symptoms like [http://en.wikipedia.org/wiki/Erythema_chronicum_migrans erythema chronicum migrans] begin to appear as well <ref name=Burgdorferi>PMID: 7043737</ref>. Studies were first conducted through New Zealand white rabbits through the use of [http://en.wikipedia.org/wiki/Immunofluorescence indirect immunofluorescence].  

These spirochetes however do not enter the host through salivary gland secretions into the blood stream. The host becomes infected because the tick's blood meal enters the gut where the spirochetes are located where some of the blood that returns to the bitten area is infected with borrelia. This results in the transmission into the host's blood stream <ref name=Onrust>PMID: 10730551</ref>). Once the bacteria is in the blood stream, the immune system may, or may not destroy this [http://en.wikipedia.org/wiki/Pathogen pathogen], depending on the presence of a [http://en.wikipedia.org/wiki/Vaccine vaccine]. The type of proteins on the surface of the borrelia detected by the host's immune system determines the fate of the survival of this disease. One of the main outer surface proteins, OspA, plays a major role in the ability of the immune system to destroy these [http://en.wikipedia.org/wiki/Antigen antigens] <ref name=Ding >PMID: 11183781</ref>.

<Structure load='1FJ1' size='400' align='left' caption='OspA (magenta, cyan) complex with antibody light chain (grey, pink) and heavy chain (gree, yellow) (PDB code [[1fj1]])' scene='OspA_L03_Group2/Default/1' />

The model presented by the Protein Data Bank is OspA containing two [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chains] or Hybridoma Antibody LA2 (chains A and C), two [http://en.wikipedia.org/wiki/Heavy_chain heavy chains] or Hyrbridoma Antibody LA2 (chains B and D), and two outer surface protein A (chains E and F). In addition, the original PDB image suggests that the C-terminal domain was unchanged by the LA-2 binding, other than minor shifts in the conformations of all 3-loops to accommodate interactions with the Fab <ref name=Ding >PMID: 11183781</ref>.   

The following is the fit mechanism where the conformations recognize LA-2 and shifts to optimize the complementary antigen combing site <ref name=Ding >PMID: 11183781</ref>. There were 49 residues from the “three loops” involved that significantly affected by LA-2 binding, through findings from NMR and crystallization <ref name=Ding >PMID: 11183781</ref>.  Residues 207 and 227 were excluded from analysis because of the peak overlap <ref name=Ding >PMID: 11183781</ref>. The portion of the protein chain detected through 15N-HSQC NMR that were affected by the binding of LA2 <ref name=Ding >PMID: 11183781</ref> was highlighted.<scene name='OspA_L03_Group2/Residues_203-220_loop1/2'>Residues 203 to 220 in "loop 1"</scene>” were represented by purple, <scene name='OspA_L03_Group2/Residues_224-233_loop2/2'>residues 224-233 in loop 2</scene> were colored green and <scene name='OspA_L03_Group2/Residues_246-257_loop3/3'>residues 247-257 in "loop 3"</scene>” were colored aqua blue The cool coloring of the residues shows the location of LA-2’s direct contact on the “3 loops”. Primary colors were used to represent <scene name='OspA_L03_Group2/Ala_208/4'>Ala-208</scene> as orange and <scene name='OspA_L03_Group2/Ala_215/4'>Ala-215</scene> as yellow in spacefills for the primary or initial identification of the LA-2 epitope on the beta-strands. The coloration of resides are all at one end, C-terminal of the isolated OspA molecule showing the side where LA-2 binds. The rest of the model were beta-sheets that were left yellow, as the neutral color, and the only alpha-helix was colored pink, to show the general overall structure of 21 anti-parrallel beta-strands to 1 alpha-helix <ref name=Ding >PMID: 11183781</ref>.