1KVF

EMP-18 Erythropoietin Receptor Agonist Peptide

Summary for 1KVF

• Entry DOI: 10.2210/pdb1kvf/pdb
• Related: 1gje 1kvg
• Descriptor: PROTEIN: EMP-18 Receptor Agonist (1 entity in total)
• Functional Keywords: beta hairpin peptide, de novo protein
• Total number of polymer chains: 1
• Total formula weight: 1867.18

Authors

Skelton, N.J.,Russell, S.,de Sauvage, F.,Cochran, A.G. (deposition date: 2002-01-25, release date: 2002-03-06, Last modification date: 2024-11-13)

Primary citation

Skelton, N.J.,Russell, S.,de Sauvage, F.,Cochran, A.G.
Amino acid determinants of beta-hairpin conformation in erythropoeitin receptor agonist peptides derived from a phage display library
J.Mol.Biol., 316:1111-1125, 2002

PubMed Abstract: 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).

PubMed: 11884148
DOI: 10.1006/jmbi.2002.5410

Experimental method

SOLUTION NMR