Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M210476200 on February 28, 2003

J. Biol. Chem., Vol. 278, Issue 18, 15595-15600, May 2, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/18/15595    most recent
M210476200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Perrin, M. H.
Right arrow Articles by Vale, W. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Perrin, M. H.
Right arrow Articles by Vale, W. W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

A Soluble Form of the First Extracellular Domain of Mouse Type 2beta Corticotropin-releasing Factor Receptor Reveals Differential Ligand Specificity*

Marilyn H. PerrinDagger , Michael R. DiGruccio, Steven C. Koerber, Jean E. Rivier§, Koichi S. Kunitake, Deborah L. Bain, Wolfgang H. Fischer, and Wylie W. Vale

From The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037

The heptahelical receptors for corticotropin-releasing factor (CRF), CRFR1 and CRFR2, display different specificities for CRF family ligands: CRF and urocortin I bind to CRFR1 with high affinity, whereas urocortin II and III bind to this receptor with very low affinities. In contrast, all the urocortins bind with high affinities, and CRF binds with lower affinity to CRFR2. The first extracellular domain (ECD1) of CRFR1 is important for ligand recognition. Here, we characterize a bacterially expressed soluble protein, ECD1-CRFR2beta , corresponding to the ECD1 of mouse CRFR2beta . The Ki values for binding to ECD1-CRFR2beta are: astressin = 10.7 (5.4-21.1) nM, urocortin I = 6.4 (4.7-8.7) nM, urocortin II = 6.9 (5.8-8.3) nM, CRF = 97 (22-430) nM, urocortin III = sauvagine >200 nM. These affinities are similar to those for binding to a chimeric receptor in which the ECD1 of CRFR2beta replaces the ECD of the type 1B activin receptor (ALK4). The ECD1-CRFR2beta possesses a disulfide arrangement identical to that of the ECD1 of CRFR1, namely Cys45-Cys70, Cys60-Cys103, and Cys84-Cys118. As determined by circular dichroism, ECD1-CRFR2beta undergoes conformational changes upon binding astressin. These data reinforce the importance of the ECD1 of CRF receptors for ligand recognition and raise the interesting possibility that different ligands having similar affinity for the full-length receptor may, nevertheless, have different affinities for microdomains of the receptor.

* This work was supported in part by National Institutes of Health Grant NIDDK 26741, the Foundation for Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Rd., La Jolla, CA 92037; Tel.: 858-453-4100; Fax: 858-558-8763; E-mail: perrin@salk.edu.

§ The Dr. Frederik Paulsen Chair in Neurosciences Professor.

A Senior Foundation for Research Investigator.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
I. Assil-Kishawi, T. A. Samra, D. F. Mierke, and A. B. Abou-Samra
Residue 17 of Sauvagine Cross-links to the First Transmembrane Domain of Corticotropin-releasing Factor Receptor 1 (CRFR1)
J. Biol. Chem., December 19, 2008; 283(51): 35644 - 35651.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. A. Pioszak, N. R. Parker, K. Suino-Powell, and H. E. Xu
Molecular Recognition of Corticotropin-releasing Factor by Its G-protein-coupled Receptor CRFR1
J. Biol. Chem., November 21, 2008; 283(47): 32900 - 32912.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. H. Perrin, C. R. R. Grace, M. R. DiGruccio, W. H. Fischer, S. K. Maji, J. P. Cantle, S. Smith, G. Manning, W. W. Vale, and R. Riek
Distinct Structural and Functional Roles of Conserved Residues in the First Extracellular Domain of Receptors for Corticotropin-releasing Factor and Related G-protein-coupled Receptors
J. Biol. Chem., December 28, 2007; 282(52): 37529 - 37536.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. R. R. Grace, M. H. Perrin, J. Gulyas, M. R. DiGruccio, J. P. Cantle, J. E. Rivier, W. W. Vale, and R. Riek
Structure of the N-terminal domain of a type B1 G protein-coupled receptor in complex with a peptide ligand
PNAS, March 20, 2007; 104(12): 4858 - 4863.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. F. Mesleh, W. A. Shirley, C. E. Heise, N. Ling, R. A. Maki, and R. P. Laura
NMR Structural Characterization of a Minimal Peptide Antagonist Bound to the Extracellular Domain of the Corticotropin-releasing Factor1 Receptor
J. Biol. Chem., March 2, 2007; 282(9): 6338 - 6346.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
M. T. Rademaker, V. A. Cameron, C. J. Charles, and A. M. Richards
Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure
Eur. Heart J., September 1, 2006; 27(17): 2088 - 2098.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. Dong, K. Hosohata, D. I. Pinon, N. Muthukumaraswamy, and L. J. Miller
Differential Spatial Approximation between Secretin and Its Receptor Residues in Active and Inactive Conformations Demonstrated by Photoaffinity Labeling
Mol. Endocrinol., July 1, 2006; 20(7): 1688 - 1698.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
E. W. Hillhouse and D. K. Grammatopoulos
The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology
Endocr. Rev., May 1, 2006; 27(3): 260 - 286.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. S. Lisenbee, M. Dong, and L. J. Miller
Paired Cysteine Mutagenesis to Establish the Pattern of Disulfide Bonds in the Functional Intact Secretin Receptor
J. Biol. Chem., April 1, 2005; 280(13): 12330 - 12338.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. M. Chen, M. H. Perrin, M. R. DiGruccio, J. M. Vaughan, B. K. Brar, C. M. Arias, K. A. Lewis, J. E. Rivier, P. E. Sawchenko, and W. W. Vale
A soluble mouse brain splice variant of type 2{alpha} corticotropin-releasing factor (CRF) receptor binds ligands and modulates their activity
PNAS, February 15, 2005; 102(7): 2620 - 2625.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. R. R. Grace, M. H. Perrin, M. R. DiGruccio, C. L. Miller, J. E. Rivier, W. W. Vale, and R. Riek
NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G protein-coupled receptor
PNAS, August 31, 2004; 101(35): 12836 - 12841.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement