Convergent recognition of the IgE binding site on the high-affinity IgE receptor.
Two structurally distinct classes of peptides were recently identified by phage display that bind the high-affinity IgE receptor, FcepsilonRI, and block IgE binding and subsequent receptor activation. Both classes adopt highly stable structures in solution, one forming a beta 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 FcepsilonRI and that their modes of interaction share a key feature of the IgE-FcepsilonRI complex, the proline/tryptophan sandwich.
Stamos
Jennifer
J
Department of Protein Engineering, Genentech, Inc., One DNA Way, South San Francisco, CA 94080 USA. star@gene.com
Eigenbrot
Charles
C
Nakamura
Gerald R
GR
Reynolds
Mark E
ME
Yin
JianPing
J
Lowman
Henry B
HB
Fairbrother
Wayne J
WJ
Starovasnik
Melissa A
MA
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017455:Receptors, IgE / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
D010455:Peptides; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E