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1kvf
From Proteopedia
(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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| - | [[Image:1kvf.gif|left|200px]]<br /><applet load="1kvf" size=" | + | [[Image:1kvf.gif|left|200px]]<br /><applet load="1kvf" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''EMP-18 Erythropoietin Receptor Agonist Peptide'''<br /> | '''EMP-18 Erythropoietin Receptor Agonist Peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Display of peptide libraries on filamentous phage has led to the | + | 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== | ==About this Structure== | ||
| - | 1KVF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1KVF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KVF OCA]. |
==Reference== | ==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11884148 11884148] | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11884148 11884148] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Cochran, A | + | [[Category: Cochran, A G.]] |
[[Category: Russell, S.]] | [[Category: Russell, S.]] | ||
| - | [[Category: Sauvage, F | + | [[Category: Sauvage, F de.]] |
| - | [[Category: Skelton, N | + | [[Category: Skelton, N J.]] |
[[Category: NH2]] | [[Category: NH2]] | ||
[[Category: beta hairpin peptide]] | [[Category: beta hairpin peptide]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:38:18 2008'' |
Revision as of 11:38, 21 February 2008
|
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 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
Page seeded by OCA on Thu Feb 21 13:38:18 2008
