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

Cordes, Frank; Kraiczy, Peter; Roversi, Pietro; Simon, Markus M.; Brade, Volker; Jahraus, Oliver; Wallis, Russell; Goodstadt, Leo; Ponting, Chris P.; Skerka, Christine; Zipfel, Peter F.; Wallich, Reinhard; Lea, Susan M.

doi:10.1016/j.ijmm.2006.01.011

Cited by 20 publications

(21 citation statements)

References 44 publications

(36 reference statements)

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“…The same membrane was also immunoblotted with rabbit anti-FlaB antibodies to ensure equal loading between all samples. (15,16,25,35,38,41,67,67,67,71). Consistent with these prior observations, we previously generated a CspA mutant in an avirulent strain of B. burgdorferi and reported that CspA confers resistance to human serum in vitro (10).…”

Section: Methodssupporting

confidence: 80%

CspA-Mediated Binding of Human Factor H Inhibits Complement Deposition and Confers Serum Resistance in Borrelia burgdorferi

et al. 2009

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Borrelia burgdorferi has developed efficient mechanisms for evading the innate immune response during mammalian infection and has been shown to be resistant to the complement-mediated bactericidal activity of human serum. It is well recognized that B. burgdorferi expresses multiple lipoproteins on its surface that bind the human complement inhibitors factor H and factor H-like protein 1 (FH/FHL-1). The binding of FH/FHL-1 on the surface of B. burgdorferi is thought to enhance its ability to evade serum-mediated killing during the acute phase of infection. One of the key B. burgdorferi FH/FHL-1 binding proteins identified thus far was designated CspA. While it is known that CspA binds FH/FHL-1, it is unclear how the interaction between CspA and FH/FHL-1 specifically enhances serum resistance. To better understand how CspA mediates serum resistance in B. burgdorferi, we inactivated cspA in a virulent strain of B. burgdorferi. An affinity ligand blot immunoassay and indirect immunofluorescence revealed that the CspA mutant does not efficiently bind human FH to its surface. Consistent with the lack of FH binding, the CspA mutant was also highly sensitive to killing by human serum. Additionally, the deposition of complement components C3, C6, and C5b-9 was enhanced on the surface of the CspA mutant compared to that of the wild-type strain. The combined data lead us to conclude that the CspA-mediated binding of human FH confers serum resistance by directly inhibiting complement deposition on the surface of B. burgdorferi.

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Section: Methodssupporting

confidence: 80%

CspA-Mediated Binding of Human Factor H Inhibits Complement Deposition and Confers Serum Resistance in Borrelia burgdorferi

et al. 2009

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“…The atomic structure reveals that region 1, encompassing amino acids 146-LEILKKNSE-154, forms a central cleft of the BbCRASP-1 homodimer, suggesting this cleft as the most probable contact site for FHL-1 and factor H (Cordes et al, 2005(Cordes et al, , 2006. In order to identify residues relevant for host factor binding, surface-exposed, charged or hydrophobic amino acids adjacent to (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…The atomic structure suggests that residues Tyr240 and Leu246 could be critical for FHL-1 and factor H binding (Cordes et al, 2005(Cordes et al, , 2006. Indeed, the mutant Y240A bound neither FHL-1 nor factor H, and mutant L246D showed significantly reduced binding (Fig.…”

Section: Article In Pressmentioning

confidence: 95%

“…The atomic structure for BbCRASP-1 shows a large cleft that is formed in the dimer interface, which includes the putative FHL-1/factor H-binding region 1 (Cordes et al, 2005). The architecture of the cleft has approximately the correct dimensions and size suitable to accommodate a globular SCR domain (Cordes et al, 2006). In the present work, selected amino acids were substituted by site-directed mutagenesis, and the corresponding recombinant fusion proteins were analyzed for ARTICLE IN PRESS ---…”

Section: Fhl-1mentioning

confidence: 99%

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Mutational analyses of the BbCRASP-1 protein of Borrelia burgdorferi identify residues relevant for the architecture and binding of host complement regulators FHL-1 and factor H

Kraiczy

Hanssen-Hübner

Kitiratschky

et al. 2009

International Journal of Medical Microbiology

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“…To date, majority of the studies are focused on the interaction between human factor H and FHBPs of Borrelia Hitherto, binding site for human fH on BbCRASP-1 molecule has been described [23,24], however, scanty reports are available, if at all, which show binding pockets for FHBPs present on fH protein from various hosts. Study of comparative binding ability of FHBPs to various domains of fH (like sushi 6-7 and sushi [19][20], depending on the host species, might be the promising way to understand fundaments of FHBPs:fH interaction.…”

Section: Discussionmentioning

confidence: 99%

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

Bhide

Pulzová

et al. 2012

Journal of Proteomics

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

Cited by 20 publications

References 44 publications

CspA-Mediated Binding of Human Factor H Inhibits Complement Deposition and Confers Serum Resistance in Borrelia burgdorferi

CspA-Mediated Binding of Human Factor H Inhibits Complement Deposition and Confers Serum Resistance in Borrelia burgdorferi

Mutational analyses of the BbCRASP-1 protein of Borrelia burgdorferi identify residues relevant for the architecture and binding of host complement regulators FHL-1 and factor H

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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