Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi.

Conference item

Borrelia burgdorferi, a spirochaete transmitted to human hosts during feeding of infected Ixodes ticks, is the causative agent of Lyme disease, the most frequent vector-borne disease in Eurasia and North America. Sporadically Lyme disease develops into a chronic, multisystemic disorder. Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). The atomic structure of BbCRASP-1, the key FHL-1/FH-binding protein of B. burgdorferi, has recently been determined. Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design.

Authors: Cordes, F; Kraiczy, P; Roversi, P; Simon, M; Brade, V

• Publication status: Published
• Journal: International journal of medical microbiology : IJMM
• Volume: 296 Suppl 40
• Issue: SUPPL. 1
• Pages: 177-184
• Publication date: 2006-05-01
• Event title: 8th International Potsdam Symposium on Tick-Borne Diseases (IPS VIII)
• DOI: 10.1016/j.ijmm.2006.01.011
• EISSN: 1618-0607
• ISSN: 1438-4221
• Keywords: Complement C3b Inactivator Proteins; Molecular Sequence Data; Complement Factor H; Bacterial Proteins; Borrelia burgdorferi; Membrane Proteins; Amino Acid Sequence; Humans; Structure-Activity Relationship; Sequence Alignment; Models, Molecular; Protein Structure, Tertiary; Binding Sites; Protein Structure, Secondary