Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab

Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab

^*Biology Department, Brookhaven National Laboratory, Building 463, Upton, NY 11973; and ^‡Division of Infectious Diseases, School of Medicine, State University of New York, Stony Brook, NY 11794

Abstract

OspA (outer surface protein A) is an abundant immunogenic lipoprotein of the Lyme disease spirochete Borrelia burgdorferi. The crystal structure of a soluble recombinant form of OspA was solved in a complex with the Fab fragment of mouse monoclonal antibody 184.1 and refined to a resolution of 1.9 Å. OspA has a repetitive antiparallel β topology with an unusual nonglobular region of “freestanding” sheet connecting globular N- and C-terminal domains. Arrays of residues with alternating charges are a predominant feature of the folding pattern in the nonglobular region. The 184.1 epitope overlaps with a well conserved surface in the N-terminal domain, and a hydrophobic cavity buried in a positively charged cleft in the C-terminal domain is a potential binding site for an unknown ligand. An exposed variable region on the C-terminal domain of OspA is predicted to be an important factor in the worldwide effectiveness of OspA-based vaccines.

Footnotes

↵ † Present address: California Institute of Technology, Division of Biology, mailcode 147–75, Pasadena, CA 91125.
↵ § To whom reprint requests should be addressed.
Paul B. Sigler, Yale University, New Haven, CT
Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, Biology Department, Brookhaven National Laboratory, Upton, NY 11973 (reference 1OSP).
ABBREVIATION:

OspA,

outer surface protein A