Open AccessNMR study of the differential contributions of residues of transforming growth factor alpha to association with its receptor
Author(s) -
Campbell McInnes,
Suzanne Grothé,
Maureen D. O’Connor-McCourt,
Brian D. Sykes
Publication year - 2000
Publication title -
protein engineering, design and selection
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.627
H-Index - 109
eISSN - 1741-0134
pISSN - 1741-0126
DOI - 10.1093/protein/13.3.143
Subject(s) - heteronuclear molecule , receptor , epitope , tgf alpha , transforming growth factor , chemistry , ligand (biochemistry) , epidermal growth factor receptor , biophysics , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy , biology , microbiology and biotechnology , genetics , antibody
A heteronuclear NMR study of human transforming growth factor alpha (TGFalpha) in complex with the epidermal growth factor receptor extracellular domain (EGFR-ED) provided an effective method for delineating the relative contributions of the residues of the ligand to its affinity for the receptor. In conjunction with previously obtained mutagenesis data, these results indicate that while a large number of residues are involved in complex formation and make up the binding interface, a small subset contribute most of the binding energy. They also show that while the residues which contribute to receptor binding are localized on one face of the molecule, the specific residues that play the major role in the affinity of TGFalpha in the complex are in two distinct regions of TGFalpha. This suggests that two small functional epitopes each composed of two residues exist within a larger structural epitope presented on the binding face. These results give the most detailed picture to date of the receptor binding determinants and yield further insight into the formation of the ligand-receptor complex.