University of Helsinki, Finland.

Abstract

Borrelia burgdorferi spirochetes that cause Lyme borreliosis survive for a long time in human serum because they successfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is needed for this since it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis. To understand this process at the molecular level we used a structural approach. First, we solved the solution structure of OspE by NMR, revealing a fold that has not been seen before in proteins involved in complement regulation. Next, we solved the X-ray structure of the complex between OspE and the factor H (FH) C-terminal domains 19 and 20 (FH19-20) at 2.83 Å resolution. The structure shows that OspE binds FH19-20 in a way similar to, but not identical with, that used by endothelial cells to bind FH via glycosaminoglycans. The observed interaction of OspE with FH19-20 allows the full function of FH in down- regulation of complement activation on the bacteria. This reveals the molecular basis for how Borrelia burgdorferi evade innate immunity, and suggests how OspE could be used as a potential vaccine antigen.

Bb-CRASP, Borrelia, Complement, Immune evasion, Microbial pathogenesis, NMR, Outer surface protein E, Protein structure, X-ray crystallography, protein complex structure