Bile salt recognition by human liver fatty acid binding protein

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Fatty acid binding proteins (FABPs) are crucial for lipid transport and metabolism.
• Liver FABP (L-FABP) binds various ligands, including fatty acids and bile acids (BAs).
• Understanding L-FABP's interaction with BAs is key to elucidating BA transport and metabolic roles.

Purpose of the Study:

• To analyze the molecular interactions between human L-FABP and nine different BAs.
• To determine the binding specificity and conformational dynamics of L-FABP-BA complexes.
• To investigate the implications for intracellular BA transport.

Main Methods:

• Heteronuclear NMR spectroscopy
• Steady-state fluorescence spectroscopy
• Mass spectrometry
• Chemical-shift perturbation analysis

Main Results:

• L-FABP binds BAs with dissociation constants in the 0.6-7 μm range.
• BA substitution patterns and side-chain conjugation influence complex conformational heterogeneity.
• Trihydroxylated BAs form monomeric complexes with L-FABP.
• Binding mechanism involves intermediates, not simple binary association.

Conclusions:

• Human L-FABP exhibits poor selectivity, acting as a universal BA binder.
• Ligand chemistry influences L-FABP binding and conformational dynamics.
• Findings provide insights into molecular determinants of BA recognition and transport.