Using X-ray crystallography, we have determined the structure of the first two short consensus repeats (SCRs) of human complement receptor (CR) 2 in complex with C3d. These studies revealed: (i) a primary site of interaction for C3d within SCR2 of CR2, (ii) a hydrophobic patch holding SCR1 to SCR2 in a rigid V-shape, (iii) a dimer formed by interactions between SCR1 of each molecule, (iv) several non-linear sequences on C3d that interact with CR2 and (v) mutations of C3d amino acids within the co-crystal interface that resulted in decreased binding. In addition, a polymorphism that results in decreased C3d binding and introduces a new glycosylation site predicted to disrupt the dimer interface was found in the New Zealand White autoimmune mouse strain. Although the co-crystal complex results are in agreement with a subset of prior studies, our additional findings, which demonstrate an extended SCR1-SCR2 structure in solution and differences in the kinetics of ligand-receptor interactions with longer forms of CR2, have suggested a more complex receptor-ligand interaction. To characterize this interaction further, several approaches directed at the determination of solution phase interactions as well as the analysis of the three-dimensional structure of CR2 alone and key CR2 mutants will be necessary.
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November 2002
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Conference Article|
November 01 2002
Structure of complement receptor (CR) 2 and CR2-C3d complexes
J. Hannan;
J. Hannan
*Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
†Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
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K. Young;
K. Young
*Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
†Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
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G. Szakonyi;
G. Szakonyi
‡Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
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M. J. Overduin;
M. J. Overduin
§Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
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S. J. Perkins;
S. J. Perkins
¶Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, University College London, London NW3 2PF, U.K.
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X. Chen;
X. Chen
‡Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
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V. M. Holers
V. M. Holers
1
*Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
†Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.
1To whom correspondence should be addressed at Department of Medicine and Immunology, Box B-115, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, U.S.A. (e-mail michael.holers@uchsc.edu)
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (6): 983–987.
Citation
J. Hannan, K. Young, G. Szakonyi, M. J. Overduin, S. J. Perkins, X. Chen, V. M. Holers; Structure of complement receptor (CR) 2 and CR2-C3d complexes. Biochem Soc Trans 1 November 2002; 30 (6): 983–987. doi: https://doi.org/10.1042/bst0300983
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