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
2012; Elsevier BV; Volume: 75; Issue: 14 Linguagem: Inglês
10.1016/j.jprot.2012.04.013
ISSN1876-7737
AutoresMangesh Bhide, Katarína Bhide, Lucia Pulzová, Marián Maďar, Patrik Mlynárčik, Elena Bencúrová, Stanislav Hreško, Rastislav Mucha,
Tópico(s)Mosquito-borne diseases and control
ResumoBorrelia 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 337HENMR341 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. This article is part of a Special Issue entitled: "Farm animal proteomics".
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