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

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• 作者：Mangesh Bhide ; Katarina Bhide ; Lucia Pulzova ; Marian Madar ; Patrik Mlynarcik ; Elena Bencurova ; Stanislav Hresko ; Rastislav Mucha
• 关键词：Cattle ; Sheep ; Pig ; Factor H ; Factor H binding protein ; Complement
• 刊名：Journal of Proteomics
• 出版年：2012
• 出版时间：19 July, 2012
• 年：2012
• 卷：75
• 期：14
• 页码：4520-4528
• 全文大小：1201 K

文摘

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 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¡±.