1GJE: Peptide Antagonist of IGFBP-1, Minimized Average Structure

Highly structured, peptide antagonists of the interaction between insulin-like growth factor 1 (IGF-I) and IGF binding protein 1 (IGFBP-1) have recently been discovered by phage display of naive peptide libraries [Lowman, H. B., et al. (1998) Biochemistry 37, 8870--8878]. We now report a detailed analysis of the features of this turn-helix peptide motif that are necessary for IGFBP-1 binding and structural integrity. Further rounds of phage randomization indicate the importance of residues contributing to a hydrophobic patch on one face of the helix. Alanine-scanning substitutions confirm that the hydrophobic residues are necessary for binding. However, structural analysis by NMR spectroscopy indicates that some of these analogues are less well folded. Structured, high-affinity analogues that lack the disulfide bond were prepared by introducing a covalent constraint between side chains at positions i and i + 7 or i + 8 within the helix. Analogues based on this scaffold demonstrate that a helical conformation is present in the bound state, and that hydrophobic side chains in this helix, and residues immediately preceding it, interact with IGFBP-1. By comparison of alanine scanning data for IGF-I and the turn-helix peptide, we propose a model for common surface features of these molecules that recognize IGFBP-1.
PDB ID: 1GJEDownload
MMDB ID: 73628
PDB Deposition Date: 2001/5/11
Updated in MMDB: 2011/10
Experimental Method:
solution nmr
Similar Structures:
Biological Unit for 1GJE: monomeric; determined by author
Molecular Components in 1GJE
Label Count Molecule
Protein (1 molecule)
Igfbp-1 Antagonist
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB