Convergent Recognition of the IgE Binding Site on the High-Affinity IgE Receptor

• Published in: Structure (London) 2004-07, Vol.12 (7), p.1289-1301
• Main Authors: Stamos, Jennifer, Eigenbrot, Charles, Nakamura, Gerald R, Reynolds, Mark E, Yin, JianPing, Lowman, Henry B, Fairbrother, Wayne J, Starovasnik, Melissa A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding, Competitive; Cells, Cultured; Crystallography, X-Ray; Humans; Immunoglobulin E - chemistry; Immunoglobulin E - metabolism; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Peptides - chemistry; Peptides - metabolism; Protein Binding; Protein Conformation; Receptors, IgE - chemistry; Receptors, IgE - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2004.04.015

Two structurally distinct classes of peptides were recently identified by phage display that bind the high-affinity IgE receptor, FcϵRI, and block IgE binding and subsequent receptor activation. Both classes adopt highly stable structures in solution, one forming a β hairpin, with the other forming a helical “zeta” structure. Despite these differences, the two classes bind competitively to the same site on the receptor. Structural analyses of both peptide-receptor complexes by NMR spectroscopy and/or X-ray crystallography reveal that the unrelated peptide scaffolds have nevertheless converged to present a similar three-dimensional surface to interact with FcϵRI and that their modes of interaction share a key feature of the IgE-FcϵRI complex, the proline/tryptophan sandwich.