Identification of residues within ligand-binding domain 1 (LBD1) of the Borrelia burgdorferi OspC protein required for function in the mammalian environment
Article first published online: 28 FEB 2010
© 2010 Blackwell Publishing Ltd
Volume 76, Issue 2, pages 393–408, April 2010
How to Cite
Earnhart, C. G., LeBlanc, D. V., Alix, K. E., Desrosiers, D. C., Radolf, J. D. and Marconi, R. T. (2010), Identification of residues within ligand-binding domain 1 (LBD1) of the Borrelia burgdorferi OspC protein required for function in the mammalian environment. Molecular Microbiology, 76: 393–408. doi: 10.1111/j.1365-2958.2010.07103.x
- Issue published online: 14 APR 2010
- Article first published online: 28 FEB 2010
- Accepted 17 February, 2010.
Borrelia burgdorferi outer surface protein C (ospC) is required for the establishment of infection in mammals. However, its precise function remains controversial. The biologically active form of OspC appears to be a homodimer. Alpha helix 1 and 1′ of the apposing monomers form a solvent-accessible pocket at the dimeric interface that presents a putative ligand-binding domain (LBD1). Here we employ site-directed and allelic-exchange mutagenesis to test the hypothesis that LBD1 is a determinant of OspC function in the mammalian environment. Substitution of residues K60, E61 and E63 which line LBD1 resulted in the loss of infectivity or influenced dissemination. Analyses of the corresponding recombinant proteins demonstrated that the loss of function was not due to structural perturbation, impaired dimer formation or the loss of plasminogen binding. This study is the first to assess the involvement of individual residues and domains of OspC in its in vivo function. The data support the hypothesis that OspC interacts with a mammalian derived ligand that is critical for survival during early infection. These results shed new light on the structure–functions relationships of OspC and challenge existing hypotheses regarding OspC function in mammals.