User:Marvin O'Neal/OspA: Difference between revisions

Acute Lyme Neuroborreliosis (LNB) is part of the second stage of Lyme disease in which the spirochete invades the peripheral and central nervous systems (CNS). Symptoms of LNB include: Bannwarth’s Syndrome, Lymphocytic Meningitis, and [http://www.rightdiagnosis.com/sym/cranial_neuritis.htm Cranial] and [http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001619/ Peripheral Neuritis]. <span style="color:red">The presence of OspA in the cerebrospinal fluid (CSF) is responsible for this complex inflammatory response in the brain that leads to the neuroborreliosis.</span>

OspA is made up of 273 residues over 21 anti-parallel β-sheets and a single α-helix. It's folded conformation is divided into three main sections: a N-terminus "sandwich," a central region comprising of several β-sheets and a C-terminus "barrel" domain.<ref name="ding">PMID: 11183781</ref> The folded regions at its ends are connected by a single β-sheet layer in the middle, giving the protein the unique shape of a dumbell.<ref name="makabe">PMID: 16823038</ref>  

There are <scene name='Studio:G2SecL03/Ospa-3loops/4' target="OspA-manip">three loops</scene> at the C-terminus of OspA that are important in binding with the LA-2 Fab antibody, whose interactions provide great insight into vaccine research and effectiveness. Within these loops, there are <scene name='Studio:G2SecL03/Ospa-3residues-nor/3' target="OspA-manip">three residues</scene> <scene name='Studio:G2SecL03/Ospa-3residues-r/2' target="OspA-manip">(show residue R-groups)</scene> where there are distinct variations between the different strains of <i>Borrelia</i> and serve as potential targets for the creation of a broader vaccine.<ref name="ding">PMID: 11183781</ref> <scene name='Studio:G2SecL03/Ospa-3loops3res/1' target="OspA-manip">(display both the three loops and three residues together)</scene>  

Loop 1 <<LOOP 1>>, (residues 203-220), is important in showing variation amongst the different strains of <i>Borrelia</i> as well as being optimally conformed for binding without steric hindrance. Loop 2 <<LOOP 2>> (residues 224-233) and Loop 3 <<LOOP 3>> (residues 246-257) are more strongly conserved than Loop 1 but also help to show some variation amongst strains. The LA-2 Fab antibody readily recognizes OspA from <i>B. burgdorferi</i>, but does not recognize that from <i>B. afzelii</i> or <i>B. garinii</i>. Between Bb. and Ba. genetic sequences are generally invariant, but two residues change between the species, ALA 208 <<ALA 208>> in Bb. is GLN in Ba., and ASN 251 <<ASN 251>> in Bb. is ALA in Ba.. Bg. has more variation and in addition to the previous two differences, has at least one more difference, where ALA 215 <<ALA 215>> in Bb. is LYS, Bg. sometimes also has a deletion at Bb.’s ALA 208. LA-2 and OspA of Bb. form a tight interface when binding, and the longer GLN sidechain found in Ba. and Bg. is more difficult to accommodate, causing less binding. A chimera that was weakly recognized by LA-2 was made with parts of loop 1 from Bb., and loops 2 and 3 from Bg. 5 Recently, a different kind of chimera has been made which combined the proximal region of Bb. and distal region of Ba., and was able to successfully protect mice from both species. 8

     <li><scene name='Studio:G2SecL03/Ospa-3residues-nor/3' target="OspA-manip">Three residues</scene> in C-terminus (Ala208, Ala215 and Asn251 in <i>B. burgdorferi</i>; also hides R-groups)