1pmx
From Proteopedia
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INSULIN-LIKE GROWTH FACTOR-I BOUND TO A PHAGE-DERIVED PEPTIDE
Contents |
Overview
The dramatic improvement in the NMR spectra of insulin-like growth factor, I (IGF-I) in the presence of a peptide identified from a phage display, library has allowed for the first time the determination of a, high-resolution solution structure for much of IGF-I. The three helices of, IGF-I in this complex have an arrangement similar to that seen in, high-resolution crystal structures of IGF-I and insulin, although there, are differences in the conformation and precise location of helix 3. A, cluster of hydrophobic and basic side chains within the turn-helix motif, of the peptide contact a hydrophobic patch on helices 1 and 3 of IGF-I., The importance of this patch for tight binding was verified using alanine, scanning mutagenesis of the peptide in two different phage display, formats. Consistent with its antagonistic activity, the peptide binds to a, region implicated by mutagenesis studies to be important for association, with IGF binding proteins (IGFBPs). The ability of the peptide to also, inhibit signaling has important implications for the manner in which IGF-I, interacts with its receptor. Interestingly, the peptide uses the same, binding site as detergent and a fragment of IGFBP-5 identified in other, IGF-I complexes. The ligand-induced structural variability of helix 3 in, these complexes suggests that exchange between such conformations may be, the source of the dynamic nature of free IGF-I and likely has functional, significance for the ability of IGF-I to recognize two signaling receptors, and six binding proteins with high affinity.
Disease
Known disease associated with this structure: Growth retardation with deafness and mental retardation due to IGF1 deficiency OMIM:[147440]
About this Structure
1PMX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Complex with a phage display-derived peptide provides insight into the function of insulin-like growth factor I., Schaffer ML, Deshayes K, Nakamura G, Sidhu S, Skelton NJ, Biochemistry. 2003 Aug 12;42(31):9324-34. PMID:12899619
Page seeded by OCA on Mon Nov 12 18:45:37 2007
