Three-Dimensional Structure of a Human Immunoglobulin With a Hinge Deletion

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-05, Vol.90 (9), p.4271-4275
• Main Authors: Guddat, Luke W., Herron, James N., Edmundson, Allen B.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibodies; Antibodies, immunoglobulins; Atoms; Binding sites; Binding Sites, Antibody; Biochemistry; Biological and medical sciences; Carbohydrate Conformation; Complement C1q - metabolism; Dimers; Disulfides; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunity (Disease); Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - genetics; Immunoglobulin Fc Fragments - chemistry; Immunoglobulin G - chemistry; Immunoglobulin G - classification; Immunoglobulin G - genetics; Immunoglobulin lambda-Chains - chemistry; Immunoglobulin lambda-Chains - genetics; Immunoglobulins; Medical research; Models, Molecular; Molecular chains; Molecular immunology; Molecular Sequence Data; Molecules; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Deletion; Structure; Tunnels; Tyrosine; X-Ray Diffraction - methods
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.9.4271

X-ray analysis at 3.2-Å resolution revealed that the Mcg IgG1 (λ chain) immunoglobulin is a compact T-shaped molecule. Because of the hinge deletion, the Fc fragment lobe is pulled tightly upward into the junction of the Fab arms. Along the molecular twofold axis, the Fab arms are joined by an interchain disulfide bond between the two light chains. The antigen combining sites consist of large irregular cavities at the tips of the Fab regions. Potential complement (C1q) binding sites on Fc are sterically shielded by the Fab arms, but putative attachment sites are accessible for docking with the FcRI receptor on human monocytes and with protein A of Staphylococcus aureus.