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| | ==EMP-18 Erythropoietin Receptor Agonist Peptide== | | ==EMP-18 Erythropoietin Receptor Agonist Peptide== |
| - | <StructureSection load='1kvf' size='340' side='right'caption='[[1kvf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1kvf' size='340' side='right'caption='[[1kvf]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1kvf]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KVF FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1kvf]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KVF FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1gje|1gje]], [[1kvg|1kvg]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1kvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvf OCA], [https://pdbe.org/1kvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kvf RCSB], [https://www.ebi.ac.uk/pdbsum/1kvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kvf ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1kvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvf OCA], [https://pdbe.org/1kvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kvf RCSB], [https://www.ebi.ac.uk/pdbsum/1kvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kvf ProSAT]</span></td></tr> |
| | </table> | | </table> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cochran, A G]] | + | [[Category: Cochran AG]] |
| - | [[Category: Russell, S]] | + | [[Category: Russell S]] |
| - | [[Category: Sauvage, F de]]
| + | [[Category: Skelton NJ]] |
| - | [[Category: Skelton, N J]] | + | [[Category: De Sauvage F]] |
| - | [[Category: Beta hairpin peptide]]
| + | |
| - | [[Category: De novo protein]] | + | |
| Structural highlights
Publication Abstract from PubMed
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).
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Skelton NJ, Russell S, de Sauvage F, Cochran AG. Amino acid determinants of beta-hairpin conformation in erythropoeitin receptor agonist peptides derived from a phage display library. J Mol Biol. 2002 Mar 8;316(5):1111-25. PMID:11884148 doi:10.1006/jmbi.2002.5410
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