2o8z
From Proteopedia
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|PDB= 2o8z |SIZE=350|CAPTION= <scene name='initialview01'>2o8z</scene> | |PDB= 2o8z |SIZE=350|CAPTION= <scene name='initialview01'>2o8z</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ACE:ACETYL GROUP'>ACE</scene> | + | |LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o8z OCA], [http://www.ebi.ac.uk/pdbsum/2o8z PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2o8z RCSB]</span> | ||
}} | }} | ||
| Line 27: | Line 30: | ||
[[Category: Mesleh, M F.]] | [[Category: Mesleh, M F.]] | ||
[[Category: Shirley, W A.]] | [[Category: Shirley, W A.]] | ||
| - | [[Category: ACE]] | ||
[[Category: crf]] | [[Category: crf]] | ||
[[Category: ecd]] | [[Category: ecd]] | ||
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[[Category: peptide ligand]] | [[Category: peptide ligand]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:14:27 2008'' |
Revision as of 01:14, 31 March 2008
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| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Bound Structure of CRF1 Extracellular Domain Antagonist
Overview
Natural peptide agonists of corticotrophin-releasing factor (CRF) receptors bind to the receptor by a two-site mechanism as follows: the carboxyl end of the ligand binds the N-terminal extracellular domain (ECD) of the receptor and the amino portion of the ligand binds the extracellular face of the seven transmembrane region. Recently, peptide antagonists homologous to the 12 C-terminal residues of CRF have been derived, which bind the CRF(1) receptor through an interaction with the ECD. Here we characterized the binding of a minimal 12-residue peptide antagonist while bound to the isolated ECD of the CRF(1) receptor. We have expressed and purified soluble and properly folded ECD independent from the seven-transmembrane region as a thioredoxin fusion protein in Escherichia coli. A model of the peptide antagonist, cyclic corticotrophin-releasing factor residues 30-41 (cCRF(30-41)), was calculated while bound to the recombinant ECD using transferred nuclear Overhauser effect spectroscopy. Although the peptide is unstructured in solution, it adopts an alpha-helical conformation when bound to the ECD. Residues of cCRF(30-41) comprising the binding interface with the ECD were mapped using saturation transfer difference NMR. Two hydrophobic residues (Met(38) and Ile(41)) as well as two amide groups (Asn(34) and the C-terminal amide) on one face of the helix defined the binding epitope of the antagonist. This epitope may be used as a starting point for development of non-peptide antagonists targeting the ECD of this receptor.
About this Structure
2O8Z is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
NMR structural characterization of a minimal peptide antagonist bound to the extracellular domain of the corticotropin-releasing factor1 receptor., Mesleh MF, Shirley WA, Heise CE, Ling N, Maki RA, Laura RP, J Biol Chem. 2007 Mar 2;282(9):6338-46. Epub 2006 Dec 27. PMID:17192263
Page seeded by OCA on Mon Mar 31 04:14:27 2008
Categories: Protein complex | Heise, C E. | Laura, R P. | Ling, N. | Maki, R A. | Mesleh, M F. | Shirley, W A. | Crf | Ecd | Extracellular domain | Gpcr | Helical | Peptide ligand
