JBC Avanti Polar Lipids

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on August 12, 2005
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
280/32/29107    most recent
M501628200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Megy, S.
Right arrow Articles by Girault, J.-P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Megy, S.
Right arrow Articles by Girault, J.-P.
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?

Papers In Press, published online ahead of print May 31, 2005
J. Biol. Chem, 10.1074/jbc.M501628200
Submitted on February 11, 2005
Revised on May 31, 2005
Accepted on May 31, 2005

STD and TRNOESY NMR studies on the conformation of the oncogenic protein beta -catenin containing the phosphorylated motif DpSGXXpS bound to the beta -TrCP protein

Simon Megy, Gildas Bertho, Josyane Gharbi-Benarous, Nathalie Evrard-Todeschi, Gael Coadou, Emmanuel Ségéral, Catherine Iehle, Eric Quéméneur, Richard Benarous, and Jean-Pierre Girault

UMR 8601 CNRS, Université René Descartes, Paris Cedex 06 75270

Corresponding Author: jean-pierre.girault{at}univ-paris5.fr

beta -TrCP is the F-box protein component of an Skp1/Cul1/F-box (SCF)-type ubiquitin ligase complex. Biochemical studies have suggested that beta -TrCP targets the oncogenic protein beta -Catenin for ubiquitination and followed by proteasome degradation. To further elucidate the basis of this interaction, a complex between a 32-residue peptide from beta -Catenin containing the phosphorylated motif DPSGXXPS (P-beta -Cat17-48) and beta -TrCP was studied using Saturation Transfer Difference (STD) Nuclear Magnetic Resonance (NMR) experiments. These experiments make it possible to identify the binding epitope of a ligand at atomic resolution. An analysis of STD spectra provided clear evidence that only a few of the 32 residues receive the largest saturation transfer. In particular, the amide protons of the residues in the phosphorylated motif appear to be in close contact to the amino acids of the beta -TrCP binding pocket. The amide and aromatic protons of the His24 and Trp25 residues also receive a significant saturation transfer. These findings are in keeping with a recently published X-ray structure of a shorter beta -Catenin fragment with the beta -TrCP1-Skp1 complex, and with the earlier findings from mutagenesis and activity assays. To better characterize the ligand-protein interaction, the bound conformation of the phosphorylated beta -Catenin peptide was obtained using TRansfer Nuclear Overhauser Effect SpectroscopY (TRNOESY) experiments. Finally, we obtained the bound structure of the phosphorylated peptide showing the protons identified by STD NMR as exposed in close proximity to the molecule surface.


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. Cell Sci.Home page
W. Xu and D. Kimelman
Mechanistic insights from structural studies of beta-catenin and its binding partners
J. Cell Sci., October 1, 2007; 120(19): 3337 - 3344.
[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
 Proc. Natl. Acad. Sci. USAHome page
C. Lobry, T. Lopez, A. Israel, and R. Weil
Negative feedback loop in T cell activation through I{kappa}B kinase-induced phosphorylation and degradation of Bcl10
PNAS, January 16, 2007; 104(3): 908 - 913.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.