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J. Biol. Chem., Vol. 280, Issue 17, 17363-17370, April 29, 2005

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Structural Investigation of Borrelia burgdorferi OspB, a BactericidalFab Target^*

Michael Becker, Jonas Bunikis¶, Barbara D. Lade, John J. Dunn, Alan G. Barbour¶, and Catherine L. Lawson||**

From the Biology Department, Brookhaven National Laboratory, Upton, New York 11973, the ^¶Departments of Microbiology & Molecular Genetics and Medicine, University of California at Irvine, College of Medicine, Irvine, California 92697, and the ^||Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854

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 topologically 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.

Received for publication, November 12, 2004 , and in revised form, February 11, 2005.

^* This work was supported by National Institutes of Health Grant R01-A137256 (to J. J. D. and C. L. L.), and by National Institutes of Health Grants AI37248 and AI24424 (to A. G. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and structure factors (code 1P4P and 1RJL) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

To whom correspondence may be addressed: Biology Dept., Bldg. 463, Brookhaven National Laboratory, P.O. Box 5000, Upton, NY 11973. Tel.: 631-344-4739; Fax: 631-344-3407; E-mail: mbecker{at}bnl.gov. ** To whom correspondence may be addressed: Dept. of Chemistry & Chemical Biology, Rutgers University, 610 Taylor Rd., Piscataway, NJ 08854. Tel.: 732-445-8074; Fax: 732-445-5312; E-mail: cathy.lawson{at}rutgers.edu.

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