Bile Acid Recognition by Mouse Ileal Bile Acid Binding Protein

Area of Science:

• Biochemistry
• Molecular Biology
• Physiology

Background:

• Ileal bile acid binding protein (I-BABP, FABP6) is crucial for bile acid homeostasis.
• Its roles in intracellular bile acid buffering and transcriptional modulation are debated.

Purpose of the Study:

• To investigate the binding energetics and selectivity of mouse I-BABP (mI-BABP) with physiological bile acids.
• To elucidate the functional significance of I-BABP in bile acid signaling.

Main Methods:

• Isothermal titration calorimetry (ITC) to analyze binding thermodynamics.
• Nuclear Magnetic Resonance (NMR) spectroscopy to determine binding site selectivity.

Main Results:

• mI-BABP exhibits weak binding affinity for the most abundant mouse bile acid, β-muricholic acid.
• mI-BABP specifically recognizes conjugated forms of cholic acid (CA) and chenodeoxycholic acid (CDCA) with high affinity.
• This specific recognition occurs even when CDCA is a minor component of the bile acid pool.

Conclusions:

• I-BABP demonstrates specific and conserved recognition of the CA:CDCA ligand combination.
• This suggests a critical role for I-BABP in regulating bile acid signaling, complementing its buffering function.