Energetic and structural effects of the Tanford transition on ligand recognition of bovine β-lactoglobulin

Bovine β-lactoglobulin, an abundant protein in whey, is a promising nanocarrier for peroral administration of drug-like hydrophobic molecules, a process that involves transit through the different acidic conditions of the human digestive tract. Among the several pH-induced conformational rearrangeme...

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Published in:Archives of biochemistry and biophysics 2021-03, Vol.699, p.108750-108750, Article 108750
Main Authors: Labra-Núñez, Alfonso, Cofas-Vargas, Luis Fernando, Gutiérrez-Magdaleno, Gabriel, Gómez-Velasco, Homero, Rodríguez-Hernández, Annia, Rodríguez-Romero, Adela, García-Hernández, Enrique
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Cattle
Crystallography, X-Ray
Hydrogen-Ion Concentration
Isothermal titration calorimetry
Lactoglobulins - chemistry
Lactoglobulins - metabolism
Ligands
Lipocalin
Molecular dynamics
Molecular Dynamics Simulation
Phase Transition
Protein Binding
Protein Conformation
Sodium Dodecyl Sulfate - chemistry
Sodium Dodecyl Sulfate - metabolism
Structural energetics
Thermodynamics
X-ray crystallography
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Summary:Bovine β-lactoglobulin, an abundant protein in whey, is a promising nanocarrier for peroral administration of drug-like hydrophobic molecules, a process that involves transit through the different acidic conditions of the human digestive tract. Among the several pH-induced conformational rearrangements that this lipocalin undergoes, the Tanford transition is particularly relevant. This transition, which occurs with a midpoint around neutral pH, involves a conformational change of the E-F loop that regulates accessibility to the primary binding site. The effect of this transition on the ligand binding properties of this protein has scarcely been explored. In this study, we carried out an energetic and structural characterization of β-lactoglobulin molecular recognition at pH values above and below the zone in which the Tanford transition occurs. The combined analysis of crystallographic, calorimetric, and molecular dynamics data sheds new light on the interplay between self-association, ligand binding, and the Tanford pre- and post-transition conformational states, revealing novel aspects underlying the molecular recognition mechanism of this enigmatic lipocalin.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2020.108750