Related ArticlesNMR Spectroscopy Reveals that Polyglutamine Binding Peptide 1 Adopts a Preferred Conformation with a Defined Hydrophobic Cluster.
Arch Biochem Biophys. 2014 Jul 4;
Authors: Ramos-Martín F, Hervás R, Vázquez MC, Laurents DV
Abstract
Several important human inherited neurodegenerative diseases are caused by "polyQ expansions", which are aberrant long repeats of glutamine residues in proteins. PolyQ binding peptide 1 (QBP1), whose minimal active core sequence is Trp-Lys-Trp-Trp-Pro-Gly-Ile-Phe, binds to expanded polyQs and blocks their ?-structure transition, aggregation and in vivo neurodegeneration. Whereas QBP1 is a widely used, commercially available product, its structure is unknown. Here, we have characterized the conformations of QBP1 and a scrambled peptide (Trp-Pro-Ile-Trp-Lys-Gly-Trp-Phe) in aqueous solution by CD, fluorescence and NMR spectroscopies. A CD maximum at 227 nm suggests the presence of rigid Trp side chains in QBP1. Based on 41 NOE-derived distance constraints, the 3D structure of QBP1 was determined. The side chains of Trp 4 and Ile 7, and to a lesser extent, those of Lys 2, Trp 3 and Phe 8, form a small hydrophobic cluster. Pro 5 and Gly 6 adopt a type II tight turn and Lys 2's ?-NH3(+) is positioned to form a favorable cation-? interaction with Trp 4's indole ring. In contrast, the scrambled QBP1 peptide, which lacks inhibitory activity, does not adopt a preferred structure. These results provide a basis for future structure-based design approaches to further optimize QBP1 for therapy.
PMID: 25009140 [PubMed - as supplied by publisher]
[NMR paper] Magic Angle Spinning NMR Reveals Sequence-Dependent Structural Plasticity, Dynamics, and the Spacer Peptide 1 Conformation in HIV-1 Capsid Protein Assemblies.
Magic Angle Spinning NMR Reveals Sequence-Dependent Structural Plasticity, Dynamics, and the Spacer Peptide 1 Conformation in HIV-1 Capsid Protein Assemblies.
Magic Angle Spinning NMR Reveals Sequence-Dependent Structural Plasticity, Dynamics, and the Spacer Peptide 1 Conformation in HIV-1 Capsid Protein Assemblies.
J Am Chem Soc. 2013 Oct 28;
Authors: Han Y, Hou G, Suiter CL, Ahn J, Byeon IJ, Lipton AS, Burton SD, Hung I, Gor'kov PL, Gan Z, Brey WW, Rice D, Gronenborn AM, Polenova TE
Abstract
A key stage in HIV-1 maturation towards...
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10-30-2013 10:44 AM
Structural Characterization of Polyglutamine Fibrils by Solid-State NMR Spectroscopy.
Structural Characterization of Polyglutamine Fibrils by Solid-State NMR Spectroscopy.
Structural Characterization of Polyglutamine Fibrils by Solid-State NMR Spectroscopy.
J Mol Biol. 2011 Jul 13;
Authors: Schneider R, Schumacher MC, Mueller H, Nand D, Klaukien V, Heise H, Riedel D, Wolf G, Behrmann E, Raunser S, Seidel R, Engelhard M, Baldus M
Protein aggregation via polyglutamine stretches occurs in a number of severe neurodegenerative diseases such as Huntington's disease. We have investigated fibrillar aggregates of polyglutamine peptides...
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07-19-2011 07:52 PM
[NMR paper] Dynamics of xenon binding inside the hydrophobic cavity of pseudo-wild-type bacteriophage T4 lysozyme explored through xenon-based NMR spectroscopy.
Dynamics of xenon binding inside the hydrophobic cavity of pseudo-wild-type bacteriophage T4 lysozyme explored through xenon-based NMR spectroscopy.
Related Articles Dynamics of xenon binding inside the hydrophobic cavity of pseudo-wild-type bacteriophage T4 lysozyme explored through xenon-based NMR spectroscopy.
J Am Chem Soc. 2005 Aug 24;127(33):11676-83
Authors: Desvaux H, Dubois L, Huber G, Quillin ML, Berthault P, Matthews BW
Wild-type bacteriophage T4 lysozyme contains a hydrophobic cavity with binding properties that have been...
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Evaluation of protein adsorption and preferred binding regions in multimodal chromato
Evaluation of protein adsorption and preferred binding regions in multimodal chromatography using NMR
Chung, W. K., Freed, A. S., Holstein, M. A., McCallum, S. A., Cramer, S. M....
Date: 2010-09-28
NMR titration experiments with labeled human ubiquitin were employed in concert with chromatographic data obtained with a library of ubiquitin mutants to study the nature of protein adsorption in multimodal (MM) chromatography. The elution order of the mutants on the MM resin was significantly different from that obtained by ion-exchange chromatography. Further, the chromatographic results...
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Evaluation of protein adsorption and preferred binding regions in multimodal chromato
Evaluation of protein adsorption and preferred binding regions in multimodal chromatography using NMR.
Related Articles Evaluation of protein adsorption and preferred binding regions in multimodal chromatography using NMR.
Proc Natl Acad Sci U S A. 2010 Sep 13;
Authors: Chung WK, Freed AS, Holstein MA, McCallum SA, Cramer SM
NMR titration experiments with labeled human ubiquitin were employed in concert with chromatographic data obtained with a library of ubiquitin mutants to study the nature of protein adsorption in multimodal (MM) chromatography....
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09-15-2010 02:26 PM
[NMR paper] NMR analysis reveals a positively charged hydrophobic domain as a common motif to bou
NMR analysis reveals a positively charged hydrophobic domain as a common motif to bound acetylcholine and d-tubocurarine.
Related Articles NMR analysis reveals a positively charged hydrophobic domain as a common motif to bound acetylcholine and d-tubocurarine.
Biochemistry. 1994 Jan 25;33(3):644-50
Authors: Fraenkel Y, Gershoni JM, Navon G
A complete 1H assignment of d-tubocurarine was carried out using 1D and 2D NMR techniques. Geometries of free acetylcholine (ACh) and d-tubocurarine were compared with those of the ligands bound to a...
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[NMR paper] NMR analysis reveals a positively charged hydrophobic domain as a common motif to bou
NMR analysis reveals a positively charged hydrophobic domain as a common motif to bound acetylcholine and d-tubocurarine.
Related Articles NMR analysis reveals a positively charged hydrophobic domain as a common motif to bound acetylcholine and d-tubocurarine.
Biochemistry. 1994 Jan 25;33(3):644-50
Authors: Fraenkel Y, Gershoni JM, Navon G
A complete 1H assignment of d-tubocurarine was carried out using 1D and 2D NMR techniques. Geometries of free acetylcholine (ACh) and d-tubocurarine were compared with those of the ligands bound to a...
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[NMR paper] Solution conformation of a peptide fragment representing a proposed RNA-binding site
Solution conformation of a peptide fragment representing a proposed RNA-binding site of a viral coat protein studied by two-dimensional NMR.
Related Articles Solution conformation of a peptide fragment representing a proposed RNA-binding site of a viral coat protein studied by two-dimensional NMR.
Biochemistry. 1991 Jun 11;30(23):5722-7
Authors: van der Graaf M, van Mierlo CP, Hemminga MA
The first 25 amino acids of the coat protein of cowpea chlorotic mottle virus are essential for binding the encapsidated RNA. Although an alpha-helical...
NMR Spectroscopy Reveals that Polyglutamine Binding Peptide 1 Adopts a Preferred Conformation with a Defined Hydrophobic Cluster.
Linear Mode
