title: Variable regions in the sushi domains 6-7 and 19-20 of factor H in animals and human lead to change in the affinity to factor H binding protein of Borrelia.
abstract: Borrelia binds host's complement regulatory factor H (fH) to evade complement attack. However, binding affinities between fH-binding-proteins (FHBPs) of Borrelia and fH from various hosts are disparate. Experiments performed to unfold the underlying molecular basis of this disparity revealed that recombinant BbCRASP-1 (major FHBP of Borrelia burgdorferi) neither interacted with sushi 6-7, nor with sushi 19-20 domains of fH in cattle and pig, however, showed binding affinity to both sushi domains of human fH, sushi 6-7 of mouse and sushi 19-20 of sheep. Further, peptide-spot assay revealed three major binding sites (sushi 6:(335-346), sushi 7:(399-410) and sushi 20:(1205-1227)) in human fH that can form BbCRASP-1:fH interface, while (337)HENMR(341) residues in sushi 6 are crucial for rigid BbCRASP-1:fH complex formation. Amino acid stretches DTIEFTCRYGYRPRTALHTFRTT in ovine sushi 19-20 and SAYWEKVYVQGQ in mouse sushi 7 were important sites for fH:BbCRASP-1 interaction. Comparative analysis of the amino acid sequences of sushi 6 of cattle, pig and human revealed that bovine and porcine fH lack methionine and arginine in HENMR pocket, that may impede formation of fH:BbCRASP-1 interface. Increasing numbers of FHBPs from animal and human pathogens are being discovered, thus results presented here can be important benchmark for study of other FHBPs:FH interactions.
authors.affiliation: Laboratory of biomedical microbiology and immunology, University of veterinary medicine and pharmacy, Kosice, Slovakia. mangeshbhide@hotmail.com
authors.forename: Mangesh
authors.initials: M
authors.lastname: Bhide
authors.forename: Katarina
authors.initials: K
authors.lastname: Bhide
authors.forename: Lucia
authors.initials: L
authors.lastname: Pulzova
authors.forename: Marian
authors.initials: M
authors.lastname: Madar
authors.forename: Patrik
authors.initials: P
authors.lastname: Mlynarcik
authors.forename: Elena
authors.initials: E
authors.lastname: Bencurova
authors.forename: Stanislav
authors.initials: S
authors.lastname: Hresko
authors.forename: Rastislav
authors.initials: R
authors.lastname: Mucha
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001898:Borrelia / Q000378:metabolism*; D002417:Cattle; D017242:Complement Factor H / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011951:Receptors, Complement / Q000737:chemistry*; D012756:Sheep; D013045:Species Specificity; D013552:Swine
chemical_list: D011951:Receptors, Complement; C044257:factor H receptors; D017242:Complement Factor H