2o8z: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2o8z.gif|left|200px]] | [[Image:2o8z.gif|left|200px]] | ||
'''Bound Structure of CRF1 Extracellular Domain Antagonist''' | {{Structure | ||
|PDB= 2o8z |SIZE=350|CAPTION= <scene name='initialview01'>2o8z</scene> | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ACE:ACETYL GROUP'>ACE</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''Bound Structure of CRF1 Extracellular Domain Antagonist''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
2O8Z is a [ | 2O8Z is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O8Z OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17192263 17192263] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Heise, C E.]] | [[Category: Heise, C E.]] | ||
| Line 26: | Line 35: | ||
[[Category: peptide ligand]] | [[Category: peptide ligand]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:56:38 2008'' | ||
Revision as of 15:56, 20 March 2008
| |||||||||||||
| 2o8z | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | ACE | ||||||||||||
| 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 Thu Mar 20 17:56:38 2008
