2o8z

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[[Image:2o8z.gif|left|200px]]
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{{STRUCTURE_2o8z| PDB=2o8z | SCENE= }}
{{STRUCTURE_2o8z| PDB=2o8z | SCENE= }}
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'''Bound Structure of CRF1 Extracellular Domain Antagonist'''
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===Bound Structure of CRF1 Extracellular Domain Antagonist===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17192263 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17192263}}
==About this Structure==
==About this Structure==
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O8Z OCA].
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Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O8Z OCA].
==Reference==
==Reference==
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[[Category: Helical]]
[[Category: Helical]]
[[Category: Peptide ligand]]
[[Category: Peptide ligand]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:28:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 18:58:48 2008''

Revision as of 15:58, 28 July 2008

Image:2o8z.png

Template:STRUCTURE 2o8z

Bound Structure of CRF1 Extracellular Domain Antagonist

Template:ABSTRACT PUBMED 17192263

About this Structure

Full experimental 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

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