The first step in the activation of the classical pathway of the complement system by immune complexes involves the binding of the six globular heads of C1q to the Fc regions of IgG or IgM. The globular heads of C1q are located C-terminal to the six triple-helical stalks present in the molecule; each head is considered to be composed of the C-terminal halves (3×136 residues) of one A-, one B- and one C-chain. It is not known if the C-terminal globular regions, present in each of the three types of chain, are independently folded modules (with each chain having distinct binding properties towards immunoglobulins) or whether the different binding functions of C1q are dependent upon a globular structure which relies on contributions from all three chains. As a first step towards addressing this question, we have expressed the globular head region (residues 87–226) of the C1q B-chain (ghB) as a soluble fusion protein with maltose-binding protein (MBP) in Escherichia coli. The affinity purified fusion protein, designated MBP–ghB, behaved as a dimer on gel filtration and bound preferentially to aggregated IgG rather than to IgM. It could also inhibit C1q-dependent haemolysis of both IgG- and IgM-sensitized erythrocytes. After its release from MBP, by use of Factor Xa, the free ghB exhibited a tendency to aggregate and come out of solution. Since MBP is known to be a monomeric molecule, the dimerization of the MBP–ghB fusion polypeptide is probably brought about by the ghB region, perhaps through hydrophobic interactions within the ghB region. The functional behaviour of MBP–ghB indicates that the globular regions of C1q may adopt a modular organization, i.e. each globular head of C1q may be composed of three structurally and functionally independent domains, thus retaining multivalency in the form of a heterotrimer.
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Research Article|
July 01 1998
Functional characterization of a recombinant form of the C-terminal, globular head region of the B-chain of human serum complement protein, C1q
Uday KISHORE;
Uday KISHORE
1Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
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Leonara E. A. LEIGH;
Leonara E. A. LEIGH
1Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
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Paul EGGLETON;
Paul EGGLETON
1Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
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Peter STRONG;
Peter STRONG
1Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
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Michael V. PERDIKOULIS;
Michael V. PERDIKOULIS
1Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
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Antony C. WILLIS;
Antony C. WILLIS
1Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
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Kenneth B. M. REID
Kenneth B. M. REID
1
1Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
1To whom correspondence should be addressed (e-mail kbmreid@bioch.ox.ac.uk).
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Publisher: Portland Press Ltd
Received:
December 19 1997
Revision Received:
March 17 1998
Accepted:
March 30 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 333 (1): 27–32.
Article history
Received:
December 19 1997
Revision Received:
March 17 1998
Accepted:
March 30 1998
Citation
Uday KISHORE, Leonara E. A. LEIGH, Paul EGGLETON, Peter STRONG, Michael V. PERDIKOULIS, Antony C. WILLIS, Kenneth B. M. REID; Functional characterization of a recombinant form of the C-terminal, globular head region of the B-chain of human serum complement protein, C1q. Biochem J 1 July 1998; 333 (1): 27–32. doi: https://doi.org/10.1042/bj3330027
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