Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab.
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 A. OspA has a repetitive antiparallel beta 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.
Li
H
H
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Dunn
J J
JJ
Luft
B J
BJ
Lawson
C L
CL
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry* / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000737:chemistry* / Q000276:immunology; D003460:Crystallization; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D008074:Lipoproteins; D008193:Lyme Disease / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007140:Immunoglobulin Fab Fragments; D008074:Lipoproteins; C072045:OspA protein