Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi.

Area of Science:

• Immunology
• Microbiology
• Structural Biology

Background:

• Borrelia burgdorferi causes Lyme borreliosis by evading the complement system, a key part of innate immunity.
• Outer surface protein E (OspE) is crucial for this evasion by recruiting complement regulator factor H (FH).

Purpose of the Study:

• To elucidate the molecular mechanism by which OspE facilitates complement evasion.
• To understand the structural basis of the interaction between OspE and factor H.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy to determine the solution structure of OspE.
• X-ray crystallography to solve the structure of the OspE-FH19-20 complex at 2.83 Å resolution.

Main Results:

• The solution structure of OspE revealed a novel fold previously unseen in complement regulation proteins.
• The crystal structure demonstrated that OspE binds to FH C-terminal domains 19 and 20 (FH19-20) similarly to, but not identically with, endothelial cell binding.
• This interaction enables factor H to effectively down-regulate complement activation on the bacterial surface.

Conclusions:

• The study reveals the molecular basis for Borrelia burgdorferi's evasion of innate immunity.
• OspE's interaction with factor H is key to bacterial survival.
• OspE presents potential as a target for vaccine development against Lyme borreliosis.