Lipid binding protein response to a bile acid library: a combined NMR and statistical approach.
Related Articles Lipid binding protein response to a bile acid library: a combined NMR and statistical approach.
FEBS J. 2015 Aug 11;
Authors: Tomaselli S, Pagano K, Boulton S, Zanzoni S, Melacini G, Molinari H, Ragona L
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]
More...