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The amino-terminal ...
The amino-terminal module of the C4b-binding protein alpha-chain is crucial for C4b binding and factor I-cofactor function
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- Härdig, Y (författare)
- Lund University,Skåne University Hospital
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- Hillarp, A (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups,Skåne University Hospital
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- Dahlbäck, B (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- Portland Press Ltd. 1997
- 1997
- Engelska.
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Ingår i: The Biochemical journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 323:Pt 2, s. 75-469
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Abstract
Ämnesord
Stäng
- C4b-binding protein (C4BP) regulates the classical pathway C3-convertase of the complement system. Human C4BP is composed of seven identical subunits (alpha-chains) and one unique one (beta-chain). Both types of chains contain homologous repeats called complement control proteins (CCPs); the alpha-chain contains eight CCPs and the beta-chain three. Each alpha-chain contains a binding site for C4b although the detailed localization of this binding site is not known. We have used three different chimeric proteins, originally designed to localize the protein S-binding site on C4BP, to demonstrate the importance of the amino-terminal part of the alpha-chain for the complement-regulatory functions of C4BP. These recombinant proteins were composed of C4BP alpha-chains with one, two or three of the amino-terminal CCPs replaced by corresponding CCPs from the C4BP beta-chain. Furthermore, seven different monoclonal antibodies were raised against C4BP and characterized using the recombinant chimeric proteins. Whereas all three recombinant chimeras bind protein S with the same affinity as plasma-purified C4BP, none of them bound to C4b. Three of the antibodies, which were found to bind to alpha-chain CCP 1 and CCP 2, completely inhibited the binding of plasma-purified C4BP to immobilized C4b. In addition, two of these antibodies totally blocked the factor I-cofactor activity of C4BP in a C4b-degradation assay. The binding site for one of the monoclonal antibodies was also studied using electron microscopy where it was confirmed that this antibody bound to the amino-terminal tip of the alpha-chain. These results show that the amino-terminal CCP of the C4BP alpha-chain (CCP 1) is crucial for the C4b binding and factor I-cofactor activity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- Animals
- Antibodies, Monoclonal/metabolism
- Anticoagulants/metabolism
- Binding, Competitive
- Complement C4b/metabolism
- Complement Factor I/metabolism
- Complement Inactivator Proteins
- Epitope Mapping
- Glycoproteins
- Humans
- Mice
- Mice, Inbred BALB C
- Microscopy, Electron
- Models, Molecular
- Protein Conformation
- Protein S/metabolism
- Receptors, Complement/chemistry
- Recombinant Fusion Proteins/chemistry
- Recombinant Proteins/chemistry
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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