Structural Basis for Complement Evasion by Lyme Disease Pathogen Borrelia burgdorferi
| Autor: | Jesper S. Oeemig, T. Sakari Jokiranta, Adrian Goldman, Hideo Iwaï, Arnab Bhattacharjee, Markus J. Lehtinen, Robert Kolodziejczyk, Taru Meri, Tommi Kajander |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Magnetic Resonance Spectroscopy
Protein Conformation Lipoproteins Immunology Molecular Sequence Data Plasma protein binding Biology Crystallography X-Ray Biochemistry Microbiology 03 medical and health sciences 0302 clinical medicine Lyme disease Immune system Borrelia medicine Humans Protein Interaction Domains and Motifs Amino Acid Sequence Borrelia burgdorferi Molecular Biology 030304 developmental biology Glycosaminoglycans 0303 health sciences Antigens Bacterial Lyme Disease Innate immune system Binding Sites Sequence Homology Amino Acid Endothelial Cells Hydrogen Bonding Cell Biology biochemical phenomena metabolism and nutrition medicine.disease biology.organism_classification bacterial infections and mycoses Virology Immunity Innate 3. Good health Complement system Factor H Complement Factor H bacteria 030215 immunology Bacterial Outer Membrane Proteins Protein Binding |
| Zdroj: | ResearcherID |
| Popis: | 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 because 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 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 B. burgdorferi evades innate immunity and suggests how OspE could be used as a potential vaccine antigen. |
| Databáze: | OpenAIRE |
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