Functional characterization of BbCRASP-2, a distinct outer membrane protein of Borrelia burgdorferi that binds host complement regulators factor H and FHL-1
Borrelia burgdorferi, the aetiological agent of Lyme disease, employs sophisticated means to survive in diverse mammalian hosts. Recent studies demonstrated that acquisition of complement regulators factor H and factor H-like protein-1 (FHL-1) allows spirochetes to resist complement-mediated killing...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
01 August 2006
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| In: |
Molecular microbiology
Year: 2006, Volume: 61, Issue: 5, Pages: 1220-1236 |
| ISSN: | 1365-2958 |
| DOI: | 10.1111/j.1365-2958.2006.05318.x |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1365-2958.2006.05318.x Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2006.05318.x 
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| Author Notes: | Kristina Hartmann, Carsten Corvey, Christine Skerka, Michael Kirschfink, Michael Karas, Volker Brade, Jennifer C. Miller, Brian Stevenson, Reinhard Wallich, Peter F. Zipfel and Peter Kraiczy |
MARC
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| 245 | 1 | 0 | |a Functional characterization of BbCRASP-2, a distinct outer membrane protein of Borrelia burgdorferi that binds host complement regulators factor H and FHL-1 |c Kristina Hartmann, Carsten Corvey, Christine Skerka, Michael Kirschfink, Michael Karas, Volker Brade, Jennifer C. Miller, Brian Stevenson, Reinhard Wallich, Peter F. Zipfel and Peter Kraiczy |
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| 520 | |a Borrelia burgdorferi, the aetiological agent of Lyme disease, employs sophisticated means to survive in diverse mammalian hosts. Recent studies demonstrated that acquisition of complement regulators factor H and factor H-like protein-1 (FHL-1) allows spirochetes to resist complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASPs) that bind factor H and/or FHL-1. In this study we have identified and characterized one of those B. burgdorferi proteins, named BbCRASP-2. BbCRASP-2 is distinct from the four previously identified factor H/FHL-1-binding CRASPs of B. burgdorferi strains. The single copy of the gene encoding BbCRASP-2, cspZ, is located on the linear plasmid lp28-3. BbCRASP-2 is highly divergent from the factor H/FHL-1-binding protein BbCRASP-1 and from members of the factor H-binding Erp (OspE/F-related) protein family. Peptide mapping analysis revealed that the factor H/FHL-1 binding site is discontinuous and it was found that C-terminal truncations abrogate factor H and FHL-1 binding. The predominant BbCRASP-2 binding site of both host complement regulators was mapped to the short consensus repeat 7 (SCR 7). Factor H and FHL-1 bound to BbCRASP-2 maintain cofactor activity for factor I-mediated C3b inactivation and accelerate the decay of the C3 convertase. Expression of BbCRASP-2 in serum-sensitive B. burgdorferi mutant B313 increased resistance to complement-mediated lysis. The characterization of BbCRASP-2 now provides a complete picture of the three diverse complement regulator-binding protein families of B. burgdorferi yielding new insights into the pathogenesis of Lyme disease. | ||
| 650 | 4 | |a Amino Acid Sequence | |
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Bacterial Proteins | |
| 650 | 4 | |a Blotting, Western | |
| 650 | 4 | |a Borrelia burgdorferi | |
| 650 | 4 | |a Complement Factor H | |
| 650 | 4 | |a Electrophoresis, Polyacrylamide Gel | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Intracellular Signaling Peptides and Proteins | |
| 650 | 4 | |a LIM Domain Proteins | |
| 650 | 4 | |a Lyme Disease | |
| 650 | 4 | |a Mass Spectrometry | |
| 650 | 4 | |a Membrane Proteins | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Mice, Inbred BALB C | |
| 650 | 4 | |a Microscopy, Fluorescence | |
| 650 | 4 | |a Molecular Sequence Data | |
| 650 | 4 | |a Muscle Proteins | |
| 650 | 4 | |a Protein Binding | |
| 650 | 4 | |a Surface Plasmon Resonance | |
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| 700 | 1 | |a Brade, Volker |e VerfasserIn |4 aut | |
| 700 | 1 | |a Miller, Jennifer C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Stevenson, Brian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wallich, Reinhard |e VerfasserIn |0 (DE-588)1059566710 |0 (DE-627)798640839 |0 (DE-576)163467781 |4 aut | |
| 700 | 1 | |a Zipfel, Peter F. |d 1954- |e VerfasserIn |0 (DE-588)110935810 |0 (DE-627)691099006 |0 (DE-576)289687810 |4 aut | |
| 700 | 1 | |a Kraiczy, Peter |e VerfasserIn |4 aut | |
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