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1kvf
From Proteopedia
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(New page: 200px<br /><applet load="1kvf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kvf" /> '''EMP-18 Erythropoietin Receptor Agonist Pepti...)
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Revision as of 23:53, 24 November 2007
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EMP-18 Erythropoietin Receptor Agonist Peptide
Overview
Display of peptide libraries on filamentous phage has led to the, identification of peptides of the form X(2-5)CX(2)GPXTWXCX(2-5) (where X, is a variable residue) that bind to the extra-cellular portion of the, erythropoietin receptor (EPO-R). These peptides adopt beta-hairpin, conformations when co-crystallized with EPO-R. Solution NMR studies reveal, that the peptide is conformationally heterogeneous in the absence of, receptor due to cis-trans isomerization about the Gly-Pro peptide bond., Replacement of the conserved threonine residue with glycine at the turn, i+3 position produces a stable beta-hairpin conformation in solution, although this peptide no longer has activity in an EPO-R-dependent cell, proliferation assay. A truncated form of the EPO-R-binding peptide, (containing the i+3 glycine residue) also forms a highly populated, monomeric beta-hairpin. In contrast, phage-derived peptide antagonists of, insulin-like growth factor binding protein 1 (IGFBP-1) have a high level, of sequence identity with the truncated EPO-R peptide (eight of 12, residues) yet adopt a turn-alpha-helix conformation in solution. Peptides, containing all possible pairwise amino acid substitutions between the, EPO-R and IGFBP-1 peptides have been analyzed to assess the degree to, which the non-conserved residues stabilize the hairpin or helix, conformation. All four residues present in the original sequence are, required for maximum population of either the beta-hairpin or alpha-helix, conformation, although some substitutions have a more dominant effect. The, results demonstrate that, within a given sequence, the observed, conformation can be dictated by a small subset of the residues (in this, case four out of 12).
About this Structure
1KVF is a Protein complex structure of sequences from [1] with NH2 as ligand. Full crystallographic information is available from OCA.
Reference
Amino acid determinants of beta-hairpin conformation in erythropoeitin receptor agonist peptides derived from a phage display library., Skelton NJ, Russell S, de Sauvage F, Cochran AG, J Mol Biol. 2002 Mar 8;316(5):1111-25. PMID:11884148
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