X-ray Crystal Structure of C3d: A C3 Fragment and Ligand for Complement Receptor 2

• DOI: 10.1126/science.280.5367.1277
• Publication Date: 2002-07-27T09:43:20Z
• Authors: Bhushan Nagar; Russell G. Jones; Russell J. Diefen...; David E. Isenman; James M. Rini
• Keywords: Models, Molecular; 0301 basic medicine; Protein Conformation; Molecular Sequence Data; Crystallography, X-Ray; Ligands; Protein Structure, Secondary; 03 medical and health sciences; Complement C3d; Mutation; Animals; Humans; Receptors, Complement 3d; Amino Acid Sequence; Sequence Alignment; Conserved Sequence

Activation and covalent attachment of complement component C3 to pathogens is the key step in complement-mediated host defense. Additionally, the antigen-bound C3d fragment interacts with complement receptor 2 (CR2; also known as CD21) on B cells and thereby contributes to the initiation of an acquired humoral response. The x-ray crystal structure of human C3d solved at 2.0 angstroms resolution reveals an α-α barrel with the residues responsible for thioester formation and covalent attachment at one end and an acidic pocket at the other. The structure supports a model whereby the transition of native C3 to its functionally active state involves the disruption of a complementary domain interface and provides insight into the basis for the interaction between C3d and CR2.