Related ArticlesNMR studies for identifying phosphopeptide ligands of the HIV-1 protein Vpu binding to the F-box protein beta-TrCP.
Peptides. 2006 Jan;27(1):194-210
Authors: Evrard-Todeschi N, Gharbi-Benarous J, Bertho G, Coadou G, Megy S, Benarous R, Girault JP
The human immunodeficiency virus type 1 (HIV-1) Vpu enhances viral particle release and, its interaction with the ubiquitin ligase SCF-beta-TrCP triggers the HIV-1 receptor CD4 degradation by the proteasome. The interaction between beta-TrCP protein and ligands containing the phosphorylated DpSGXXpS motif plays a key role for the development of severe disease states, such as HIV or cancer. This study examines the binding and conformation of phosphopeptides (P1, LIERAEDpSG and P2, EDpSGNEpSE) from HIV protein Vpu to beta-TrCP with the objective of defining the minimum length of peptide needed for effective binding. The screening step can be analyzed by NMR spectroscopy, in particular, saturation transfer NMR methods clearly identify the residues in the peptide that make direct contact with beta-TrCP protein when bound. An analysis of saturation transfer difference (STD) spectra provided clear evidence that the two peptides efficiently bound beta-TrCP receptor protein. To better characterize the ligand-protein interaction, the bound conformation of the phosphorylated peptides was determined using transferred NOESY methods, which gave rise to a well-defined structure. P1 and P2 can fold in a bend arrangement for the DpSG motif, showing the protons identified by STD-NMR as exposed in close proximity at the molecule surface. Ser phosphorylation allows electrostatic interaction and hydrogen bond with the amino acids of the beta-TrCP binding pocket. The upstream LIER hydrophobic region was also essential in binding to a hydrophobic pocket of the beta-TrCP WD domain. These findings are in good agreement with a recently published X-ray structure of a shorter beta-Catenin fragment with the beta-TrCP complex.
NMR Applications for Identifying ?-TrCP Protein-Ligand Interactions.
NMR Applications for Identifying ?-TrCP Protein-Ligand Interactions.
NMR Applications for Identifying ?-TrCP Protein-Ligand Interactions.
Mini Rev Med Chem. 2011 Jan 11;
Authors: Pons J, Tanchou V, Girault JP, Bertho G, Evrard-Todeschi N
Without crystallographic data, NMR has emerged as the best way to define protein-ligand interactions. Using NMR experiments based on magnetization transfer, one can select molecules bound, estimate the dissociation constant, identify contacts implied in the binding, obtain a structure of the bound ligand and make...
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[NMR paper] STD and TRNOESY NMR studies on the conformation of the oncogenic protein beta-catenin
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.
Related Articles 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.
J Biol Chem. 2005 Aug 12;280(32):29107-16
Authors: Megy S, Bertho G, Gharbi-Benarous J, Evrard-Todeschi N, Coadou G, Ségéral E, Iehle C, Quéméneur E, Benarous R, Girault JP
beta-TrCP is the F-box protein...
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[NMR paper] NMR techniques for identifying the interface of a larger protein-protein complex: cro
NMR techniques for identifying the interface of a larger protein-protein complex: cross-saturation and transferred cross-saturation experiments.
Related Articles NMR techniques for identifying the interface of a larger protein-protein complex: cross-saturation and transferred cross-saturation experiments.
Methods Enzymol. 2005;394:483-506
Authors: Shimada I
NMR provides detailed structural information for protein complexes with molecular weights up to 30 kDa. However, it is difficult to obtain such information on larger proteins using NMR. To...
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[NMR paper] Hydrogen bonding on the ice-binding face of a beta-helical antifreeze protein indicat
Hydrogen bonding on the ice-binding face of a beta-helical antifreeze protein indicated by amide proton NMR chemical shifts.
Related Articles Hydrogen bonding on the ice-binding face of a beta-helical antifreeze protein indicated by amide proton NMR chemical shifts.
Biochemistry. 2004 Oct 19;43(41):13012-7
Authors: Daley ME, Graether SP, Sykes BD
The dependence of amide proton chemical shifts on temperature is used as an indication of the hydrogen bonding properties in a protein. The amide proton temperature coefficients of the beta-helical...
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[NMR paper] NMR spectroscopy techniques for screening and identifying ligand binding to protein r
NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors.
Related Articles NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors.
Angew Chem Int Ed Engl. 2003 Feb 24;42(8):864-90
Authors: Meyer B, Peters T
Binding events of ligands to receptors are the key for an understanding of biological processes. Gaining insight into protein-protein and protein-ligand interactions in solution has recently become possible on an atomic level by new NMR spectroscopic techniques....
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[NMR paper] 15N and 13C NMR studies of ligands bound to the 280,000-dalton protein porphobilinoge
15N and 13C NMR studies of ligands bound to the 280,000-dalton protein porphobilinogen synthase elucidate the structures of enzyme-bound product and a Schiff base intermediate.
Related Articles 15N and 13C NMR studies of ligands bound to the 280,000-dalton protein porphobilinogen synthase elucidate the structures of enzyme-bound product and a Schiff base intermediate.
Biochemistry. 1990 Sep 11;29(36):8345-50
Authors: Jaffe EK, Markham GD, Rajagopalan JS
Porphobilinogen synthase (PBGS) catalyzes the asymmetric condensation of two molecules of...
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[NMR paper] NMR studies of retinoid-protein interactions: the conformation of [13C]-beta-ionones
NMR studies of retinoid-protein interactions: the conformation of -beta-ionones bound to beta-lactoglobulin B.
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Pharm Res. 1999 May;16(5):651-9
Authors: Curley RW, Sundaram AK, Fowble JW, Abildgaard F, Westler WM, Markley JL
PURPOSE: Vitamin A (retinol) and its metabolites comprise the natural retinoids. While the biological action of these molecules are thought to be primarily mediated by ca. 55 kDa nuclear retinoic...
NMR studies for identifying phosphopeptide ligands of the HIV-1 protein Vpu binding to the F-box protein beta-TrCP.
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