NDLI: NMR Study of the Transforming Growth Factor-α (TGF-α)-Epidermal Growth Factor Receptor Complex VISUALIZATION OF HUMAN TGF-α BINDING DETERMINANTS THROUGH NUCLEAR OVERHAUSER ENHANCEMENT ANALYSIS

Content Provider	Journal of Biological Chemistry (JBC)
Author	McInnes, Campbell Hoyt, David W. Harkins, Richard N. Pagila, Rene N. Debanne, Maria T. O'Connor-McCourt, Maureen Sykes, Brian D.
Abstract	The study of human transforming growth factor-α (TGF-α) in complex with the epidermal growth factor (EGF) receptor extracellular domain has been undertaken in order to generate information on the interactions of these molecules. Analysis of 1H NMR transferred nuclear Overhauser enhancement data for titration of the ligand with the receptor has yielded specific data on the residues of the growth factor involved in contact with the larger protein. Significant increases and decreases in nuclear Overhauser enhancement cross-peak intensity occur upon complexation, and interpretation of these changes indicates that residues of the A- and C-loops of TGF-α form the major binding interface, while the B-loop provides a structural scaffold for this site. These results corroborate the conclusions from NMR relaxation studies (Hoyt, D. W., Harkins, R. N., Debanne, M. T., O'Connor-McCourt, M., and Sykes, B. D. (1994) Biochemistry 33, 15283-15292), which suggest that the C-terminal residues of the polypeptide are immobilized upon receptor binding, while the N terminus of the molecule retains considerable flexibility, and are consistent with structure-function studies of the TGF-α/EGF system indicating a multidomain binding model. These results give a visualization, for the first time, of native TGF-α in complex with the EGF receptor and generate a picture of the ligand-binding site based upon the intact molecule. This will undoubtedly be of utility in the structure-based design of TGF-α/EGF agonists and/or antagonists.
Related Links	http://www.jbc.org/content/271/50/32204.abstract
Ending Page	32211
Starting Page	32204
Page Count	8
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	50
Volume Number	271
DOI	10.1074/jbc.271.50.32204
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	1996-12-13
Access Restriction	Open
Subject Keyword	Protein Chemistry and Structure
Alternative Title	NMR Study of the Transforming Growth Factor-α (TGF-α)-Epidermal Growth Factor Receptor Complex
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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