Abstract
Primary bile acids, differing in the hydroxylation pattern, are synthesized from cholesterol in the liver and, once formed, can undergo extensive enzyme-catalyzed glycine/taurine conjugation, giving rise to a complex mixture, the bile acid pool. Composition and concentration of the bile acid pool may be altered in diseases, posing a general question on the response of the carrier (bile acid binding protein) to the binding of ligands with different hydrophobic and steric profiles. A collection of NMR experiments (H/D exchange, Het-SOFAST, ePHOGSY-NOESY/ROESY and (15) N relaxation measurements) was thus performed on apo and five different holo proteins, to monitor the binding pocket accessibility and dynamics. The ensemble of obtained data could be rationalised by a statistical approach, based on chemical shift covariance analysis, in term of residue-specific correlations and collective protein response to ligand binding. The results indicate that the same residues are influenced by diverse chemical stresses: ligand binding always induces silencing of motions at the protein portal with a concomitant conformational rearrangement of a network of residues, located at the protein anti-portal region. This network of amino acids, which do not belong to the binding site, forms a contiguous surface, sensing the presence of the bound lipids, with a signalling role in switching on and off protein/membrane interactions. This article is protected by copyright. All rights reserved.
PMID: 26260520 [PubMed - as supplied by publisher]
[NMR paper] A Combined NMR and Computational Approach to Investigate Peptide Binding to a Designed Armadillo Repeat Protein.
A Combined NMR and Computational Approach to Investigate Peptide Binding to a Designed Armadillo Repeat Protein.
A Combined NMR and Computational Approach to Investigate Peptide Binding to a Designed Armadillo Repeat Protein.
J Mol Biol. 2015 Mar 24;
Authors: Ewald C, Christen MT, Watson RP, Mihajlovic M, Zhou T, Honegger A, Plückthun A, Caflisch A, Zerbe O
Abstract
The specific recognition of peptide sequences by proteins plays an important role both in biology and in diagnostic applications. Here we characterize the...
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A Combined NMR and Computational Approach to Investigate Peptide Binding to a Designed Armadillo Repeat Protein
A Combined NMR and Computational Approach to Investigate Peptide Binding to a Designed Armadillo Repeat Protein
Publication date: Available online 24 March 2015
Source:Journal of Molecular Biology</br>
Author(s): Christina Ewald , Martin T. Christen , Randall P. Watson , Maja Mihajlovic , Ting Zhou , Annemarie Honegger , Andreas Plückthun , Amedeo Caflisch , Oliver Zerbe</br>
The specific recognition of peptide sequences by proteins plays an important role both in biology and in diagnostic applications. Here we characterize the relatively weak binding of the...
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Residual interactions in unfolded bile acid-binding protein by (19) F NMR.
Residual interactions in unfolded bile acid-binding protein by (19) F NMR.
Residual interactions in unfolded bile acid-binding protein by (19) F NMR.
Protein Sci. 2011 Feb;20(2):327-35
Authors: Basehore HK, Ropson IJ
The folding initiation mechanism of human bile acid-binding protein (BABP) has been examined by (19) F NMR. Equilibrium unfolding studies of BABP labeled with fluorine at all eight of its phenylalanine residues showed that at least two sites experience changes in solvent exposure at high denaturant concentrations. Peak...
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[NMR paper] An AMBER/DYANA/MOLMOL phosphorylated amino acid library set and incorporation into NMR structure calculations.
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J Biomol NMR. 2005 Sep;33(1):15-24
Authors: Craft JW, Legge GB
Protein structure determination using Nuclear Magnetic Resonance (NMR) requires the use of molecular dynamics programs that incorporate both NMR experimental and implicit atomic data. Atomic parameters for each amino acid type are encoded in...
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Residual interactions in unfolded bile acid-binding protein by (19)F-NMR.
Residual interactions in unfolded bile acid-binding protein by (19)F-NMR.
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Protein Sci. 2010 Nov 29;
Authors: Basehore HK, Ropson IJ
The folding initiation mechanism of human bile acid-binding protein (BABP) has been examined by (19)F-NMR. Equilibrium unfolding studies of BABP labeled with fluorine at all eight of its phenylalanine residues showed that at least two sites experience changes in solvent exposure at high denaturant concentrations. Peak assignments...
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[NMR paper] Identification of the bile acid-binding site of the ileal lipid-binding protein by ph
Identification of the bile acid-binding site of the ileal lipid-binding protein by photoaffinity labeling, matrix-assisted laser desorption ionization-mass spectrometry, and NMR structure.
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J Biol Chem. 2001 Mar 9;276(10):7291-301
Authors: Kramer W, Sauber K, Baringhaus KH, Kurz M, Stengelin S, Lange G, Corsiero D, Girbig F, König W, Weyland C
...
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11-19-2010 08:29 PM
[NMR paper] Ligand binding alters the backbone mobility of intestinal fatty acid-binding protein
Ligand binding alters the backbone mobility of intestinal fatty acid-binding protein as monitored by 15N NMR relaxation and 1H exchange.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles Ligand binding alters the backbone mobility of intestinal fatty acid-binding protein as monitored by 15N NMR relaxation and 1H exchange.
Biochemistry. 1997 Feb 25;36(8):2278-90
Authors: Hodsdon ME, Cistola DP
The backbone dynamics of the liganded (holo) and unliganded (apo) forms of Escherichia...
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08-22-2010 03:03 PM
[NMR paper] Identification of trapped and boundary lipid binding sites in M13 coat protein/lipid
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Biochemistry. 1990 Apr 24;29(16):3828-34
Authors: Van Gorkom LC, Horváth LI, Hemminga MA, Sternberg B, Watts A
The major coat protein of M13 bacteriophage has been incorporated into bilayers of 1,2-dimyristoyl-sn-glycero-3-phosphocholine, deuterated in the trimethyl segments of...