Structural Investigation ofBorrelia burgdorferiOspB, a BactericidalFab Target

Michael Becker, Jonas Bunikis, Barbara D. Lade, John J. Dunn, Alan G. Barbour, Catherine L. Lawson
2005 Journal of Biological Chemistry  
Certain antibody Fab fragments directed against the C terminus of outer surface protein B (OspB), a major lipoprotein of the Lyme disease spirochete, Borrelia burgdorferi, have the unusual property of being bactericidal even in the absence of complement. We report here x-ray crystal structures of a C-terminal fragment of B. burgdorferi OspB, which spans residues 152-296, alone at 2.0-Å resolution, and in a complex with the bactericidal Fab H6831 at 2.6-Å resolution. The H6831 epitope is
more » ... cally analogous to the LA-2 epitope of OspA and is centered around OspB Lys-253, a residue essential for H6831 recognition. A ␤-sheet present in the free OspB fragment is either disordered or removed by proteolysis in the H6831-bound complex. Other conformational changes between free and H6831-bound structures are minor and appear to be related to this loss. In both crystal structures, OspB C-terminal fragments form artificial dimers connected by intermolecular ␤-sheets. OspB structure, stability, and possible mechanisms of killing by H6831 and other bactericidal Fabs are discussed in light of the structural data.
doi:10.1074/jbc.m412842200 pmid:15713683 fatcat:wx3w6olhgvaoriuqdyy6itkdtm