G15SecL05Tpc3

From Proteopedia

Revision as of 19:15, 14 August 2012

Outer Surface Protein B (Osp-B) of the Borrelia burgdorferi Spirochete Bacterium (Title)

is a primary outer-surface lipoprotein molecule found in the Lyme disease spirochete Borrelia burgdorferi, a molecule essential for the survival of the bacterium. Since its primary function is to serve both as a site of antibody recognition and as the microvillar attachment to the Ixodes scapularis midgut, it is constitutively expressed.

Structure

Significance in Lyme Disease and Bind Briefing

Lyme disease is a bacterial infectious disease of the skin, joints, nervous system and heart dominantly caused by the spirochete Borrelia burgdorferi, transmitted to humans via the bite of the deer tick Ixodes scapularis (Becker, 2005). The importance of antibodies in controlling such spirochaetal infections was underscored by the discovery of two particular antibodies with distinctive bactericidal properties: the monoclonal antibodies CB2 and H6831 (Connoly, Benach). When directed against the C-terminus of the outer-surface protein Osp-B, these fragments are bactericidal even in the absence of complements or phagocytes (Sadziene, 1994). The formation of the OspB-CB2 and OspB-H6831 complexes were dependent upon a single lysine residue in Osp-B, Lys 253 (GREEN LINK THAT), for binding and thus leading to lysis of the outer membrane of the spirochete; the structural changes that result culminate into molecular instability and protease susceptibility that eventually lead to said lysis, though the exact physiological consequences of these changes are not yet fully sequenced nor understood (Connoly, Benach). These antibodies demonstrate enormous selective pressure; growth of Borrelia burgdorferi spirochetes in their presence generated escape mutants that lacked the critical Lys 253 amino acid on Osp-B for antibody binding, and were thus less infectious in experimental mouse models and in vitro experimental assays (Connoly, Benach).

Osp-B/Antibody Binding Processes

Complement-independent antibodies have the ability to attack antigens directly in the absece of both complements or phagocytes. The exact mechanisms for these processes have not yet been clearly defined, though basic evidence shows that the attack of the complement-independent antibody creates a vesicle outgrowth that leads to an opening in the outer layer of the bacteria which leads to an osmotic lysis. (LaRocca et al 2009). The monoclonal CB2 antibody binds to the Osp-B protein of the spirochete bacteria: its high affinity toward the Borrelia's epitope binding site eliminates the bacteria accordingly. Selective pressure has led to multiple Borrelia bacterium escaping this occurrence due possible point mutations at the C-terminus end of the Osp-B lipoprotein; namely, an absence of the Lys 253 amino acid which promotes the binding affinity. The antigen variation of borrelias inept the binding affinity of the antibody to the epitope located on the OspB.

H6831

Related Structures

• Crystal structure of the C-terminal fragment
• OspB-H6831 Complex
• CB2

Links

• Lyme Disease CDC Lyme Disease Webpage
• Borrelia burgdorferi
• Ixodes Dammini

Notes and Literature References

• 1. Becker, M., Bunikis, J., Lade, B.D, Dunn, J.J., Barbour, A.G., Lawson, C.L. “Structural Investigation of Borrelia burgdorferi OspB, a BactericidalFab Target” The Journal of Biological Chemistry; Vol. 280, No.17, issue of April 29, pp. 17363- 17370, 2005
• 2. Connolly, S.E., Benach, J.L. “The Versatile Roles of Antibodies in Borrelia Infections” Nature Reviews: Microbiology, Volume 3, May 2005, pp. 411-420
• 3. LaRocca, T.J., Benach, J.L. 2008 “The Important and Diverse Roles of Antibodies in the Host Response to Borrelia Infections” Specialization and Complementation of Humoral Immune Responses to in Infection. Current Topics in Microbiology and Immunology 319