Structural models for carcinoembryonic antigen and its complex with the single-chain Fv antibody molecule MFE23

• Published in: FEBS letters 2000-06, Vol.475 (1), p.11-16
• Main Authors: Boehm, Mark K., Perkins, Stephen J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibody; Carcinoembryonic antigen; Carcinoembryonic Antigen - chemistry; Carcinoembryonic Antigen - metabolism; CEA, carcinoembryonic antigen; CEA-1 to CEA-7, domain numbering in CEA; H1-H120 and L1-L106, sequence numbering of MFE23 heavy and light chains respectively; H1-H3 and L1-L3, antigen-binding loops of MFE23; Homology model; Humans; ICAM-2, intercellular cell adhesion molecule-2; Ig, immunoglobulin; Immunoglobulin Fragments - chemistry; Immunoglobulin Fragments - metabolism; Models, Molecular; Molecular Sequence Data; PDB, protein data bank; Protein Binding; Protein Conformation; Scattering; Single-chain Fv; Structure prediction; VCAM-1, vascular cell adhesion molecule; VH, variable heavy chain domain; VL, variable light chain domain
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)01612-4

MFE23 is a single chain Fv antibody that has a high affinity for carcinoembryonic antigen (CEA). A full homology model for CEA based on V-type, I-type and C2-type immunoglobulin folds, 28 oligosaccharides and the interdomain angle of CD2 was validated using solution scattering data. The superimposition of the intermolecular contacts observed in our recent crystal structure of MFE23 with the N-terminal domain of CEA permitted the MFE23–CEA complex to be modelled. Good surface and electrostatic complementarity and carbohydrate-unhindered access of MFE23 with the indentation between the first two CEA domains was observed. The model is supported by biochemical data and provides insight on the high affinity of MFE23 for CEA.