title: Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi.
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 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.
authors: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, FIN-00014 Helsinki, Finland.
authors: Arnab
authors: A
authors: Bhattacharjee
authors: Jesper S
authors: JS
authors: Oeemig
authors: Robert
authors: R
authors: Kolodziejczyk
authors: Taru
authors: T
authors: Meri
authors: Tommi
authors: T
authors: Kajander
authors: Markus J
authors: MJ
authors: Lehtinen
authors: Hideo
authors: H
authors: Iwaï
authors: T Sakari
authors: TS
authors: Jokiranta
authors: Adrian
authors: A
authors: Goldman
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001665:Binding Sites; D025065:Borrelia burgdorferi / Q000276:immunology*; D017242:Complement Factor H / Q000276:immunology*; D018360:Crystallography, X-Ray; D042783:Endothelial Cells / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D007113:Immunity, Innate; D008074:Lipoproteins / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D017386:Sequence Homology, Amino Acid
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D006025:Glycosaminoglycans; D008074:Lipoproteins; C084998:OspE protein, Borrelia burgdorferi; D017242:Complement Factor H
keywords: Bb-CRASP; Borrelia; Complement; Immune Evasion; Microbial Pathogenesis; NMR; Outer Surface Protein E; Protein Complex Structure; Protein Structure; X-ray Crystallography
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