A crystal structure of the complex between human complement receptor 2 and its ligand C3d
Jean M H van den Elsen1, David E Isenman
1Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK. bssjmhve@bath.ac.uk
Science (New York, N.Y.)
|April 30, 2011
Summary
Complement receptor 2 (CR2) binding to C3d enhances antibody responses. A new cocrystal structure reveals the correct CR2-C3d interaction interface, crucial for immune system links and potential therapeutic applications.
Area of Science:
- Immunology
- Structural Biology
- Biochemistry
Background:
- Complement receptor 2 (CR2) on B cells and follicular dendritic cells interacts with C3d, enhancing antibody responses.
- This interaction bridges innate and adaptive immunity.
- Previous CR2-C3d cocrystal structures showed discrepancies with biochemical data regarding the binding interface.
Purpose of the Study:
- To resolve controversies surrounding the CR2-C3d binding interface.
- To determine the accurate structural basis of CR2-C3d interaction.
- To provide insights for vaccine design and autoimmune disease therapeutics.
Main Methods:
- Cocrystallization of the CR2(SCR1-2):C3d complex.
- X-ray diffraction to determine the structure at 3.2 angstrom resolution.
Main Results:
- A novel cocrystal structure of the CR2(SCR1-2):C3d complex was determined.
- The identified interaction interfaces differ significantly from a previously reported structure.
- The new structure is consistent with existing biochemical data, suggesting the previous structure may have been influenced by crystallization additives.
Conclusions:
- The study provides an accurate structural model of the CR2-C3d interaction.
- This detailed understanding of the binding interface can inform the development of new vaccines.
- The findings offer potential for designing therapeutics targeting autoreactive B cells.
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