Structural investigation of Borrelia burgdorferi OspB, a bactericidal Fab target.
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-A resolution, and in a complex with the bactericidal Fab H6831 at 2.6-A resolution. The H6831 epitope is topologically analogous to the LA-2 epitope of OspA and is centered around OspB Lys-253, a residue essential for H6831 recognition. A beta-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 beta-sheets. OspB structure, stability, and possible mechanisms of killing by H6831 and other bactericidal Fabs are discussed in light of the structural data.
Becker
Michael
M
Biology Department, Brookhaven National Laboratory, Upton, New York 11973, USA. mbecker@bnl.gov
Bunikis
Jonas
J
Lade
Barbara D
BD
Dunn
John J
JJ
Barbour
Alan G
AG
Lawson
Catherine L
CL
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism*; D000954:Antigens, Surface / Q000737:chemistry; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000378:metabolism*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019281:Dimerization; D000939:Epitopes / Q000737:chemistry; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014357:Trypsin / Q000737:chemistry; D014961:X-Ray Diffraction
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D008074:Lipoproteins; C077030:OspB protein, Borrelia burgdorferi; D014357:Trypsin