OspA L03 Group2
From Proteopedia
| Line 28: | Line 28: | ||
<scene name='OspA_L03_Group2/Default/1'>Restore to default</scene> | <scene name='OspA_L03_Group2/Default/1'>Restore to default</scene> | ||
| - | + | <Structure load='1FJ1' size='400' align='left' caption='Structure of OspA (PDB entry[[1FJ1]])' scene='OspA_L03_Group2/Default/1'> | |
| - | <Structure load='1FJ1' size='400' align='left' caption='Structure of OspA (PDB entry[[1FJ1]])'scene= | + | |
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 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>. | ||
| Line 36: | Line 35: | ||
The following is the fit mechanism where the conformations recognize LA-2 and shifts to optimize the complementary antigen combing site (Ding, 2000). 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 pale green, <scene name='OspA_L03_Group2/Residues_224-233_loop2/2'>residues 224-233 in loop 2</scene> were colored purple and <scene name='OspA_L03_Group2/Residues_246-257_loop3/3'>residues 247-257 in "loop 3"</scene>” were colored medium slate 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 red and <scene name='OspA_L03_Group2/Ala_215/4'>Ala-215</scene> as blue 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>. | The following is the fit mechanism where the conformations recognize LA-2 and shifts to optimize the complementary antigen combing site (Ding, 2000). 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 pale green, <scene name='OspA_L03_Group2/Residues_224-233_loop2/2'>residues 224-233 in loop 2</scene> were colored purple and <scene name='OspA_L03_Group2/Residues_246-257_loop3/3'>residues 247-257 in "loop 3"</scene>” were colored medium slate 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 red and <scene name='OspA_L03_Group2/Ala_215/4'>Ala-215</scene> as blue 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>. | ||
| + | |||
Revision as of 22:55, 15 August 2012
Contents |
Introduction
Spirochetes and Lyme Disease
First recognized in 1957, Lyme disease has been estimated to affect between 20 and 100 cases per 100,000 individuals in the United States (Rupprecht, 2008). This bacterial vector of spirochetes, called Borrelia burgdorferi, was found on the gut of the Ixodes tick (Burgdorfer, 1982). The bacteria spread through the bite of the tick forming severe skin lesions. Other health complications include chronic arthritis, and neurologic and cardiac abnormalities (Burgdorferi, 1982). From 10-12 weeks of infestation, other symptoms like erythema chronicum migrans begin to appear as well(Burgdorferi, 1982). Studies were first conducted through New Zealand white rabbits (Burgdorferi, 1982) through the use of indirect immunofluorescence.
Outer surface proteins
There are outer surface protein A, B, and C. Specifically, outer surface protein A, or OspA is found to inhibit bacterial transmission [1]. Outer surface protein A, or OspA was found to initiate an immune response that contributed towards the development of Lyme disease vaccinations. It prevented the transmission of Borrelia_burgdorferi, the causative bacterial agent of Lyme disease after the attachment of an infected tick [1].
About OspA
OspA is a lipoprotein found on the outer surface of the bacteria that is found to inhibit bacterial transmission [1]. In order for Lyme Disease to start and progress in the human or animal body, the initial levels of OspA is underregulated, inactivated, hidden, or OspA negative [1]. The bacteria underregulates OspA for the reason that it does not want to trigger any innate immune response from the host [1]. Experiments that showed the success of the Borrelia bacteria progressing in the body, were done through mice. Only OspA- positive borrelia admitted to apoptosis in the host; therefore, when the outer surface protein was present the Borrelia bacteria cannot survive [1]. Unless the vaccine with OspA is administered, or the bacteria has moved to a different environment of the cerebrospinal fluid or an inflammatory environment, the bacteria will activate and start to regulate OspA [1] by activating B-cells. Later this induced astrogliosis.
The whole system of OspA on the antigen interacting with the antibodies was a cascade complement system. Once the complement found OspA on borrelia, it induced an innate response of phagocytosis. Not only did OspA allowed opsonization, but also attracted leukocytes ([1].
Pathology of OspA
Once entered the host through the skin or blood stream, Borrelia burgdorferi downregulated and suppressed OspA to minimize all of the host’s immunogenic characteristics [2]. When OspA on the spirochete migrated to an inflammatory environment, it induced apoptosis on the bacteria through the activation of B-cells [2]. Only OspA positive in borrelia bacteria were unable to establish an infection compared to OspA negative bacteria successfully hosted in studies of mice [2]. OspA known as a potent stimulator of neutrophils was able to kill the pathogen and attract leukocytes allowing the release of proinflammatory cytokines in a host [2] and avoid contracting Lyme disease as it affects the heart, joints, and central nervous system [2]. The reactive LA-2 antibody was found to serve as an important epitope of Osp-A binding [1] towards developing vaccinations. The free state of the 3D model exposed the C-terminal where there were 49 residues from the “three loops” involved that significantly affected by LA-2 binding, through findings from nuclear magnetic resonance, or NMR and crystallization [1].
Structure
| |||||||||||
