IFABP portal region insertion during membrane interaction depends on phospholipid composition

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Intestinal fatty acid-binding protein (IFABP) is crucial for lipid metabolism in the intestinal epithelium.
• FABPs regulate lipid availability, trafficking, and targeting within cells.
• Understanding IFABP's membrane interaction is key to its function.

Purpose of the Study:

• To characterize the interaction of IFABP with phospholipid membranes.
• To investigate the role of the IFABP portal domain in membrane penetration.
• To determine how lipid composition affects IFABP's membrane immersion.

Main Methods:

• Construction of tryptophan (Trp)-mutants of IFABP.
• Utilized fluorescent techniques with selective quenching agents.
• Employed vesicles with varying lipid compositions, including cardiolipin (CL).

Main Results:

• The portal region of IFABP penetrates deeply into the hydrophobic core of phospholipid bilayers.
• Penetration is enhanced with cardiolipin-containing vesicles.
• Protein orientation and penetration depth depend on lipid composition, net charge, and ionic strength.

Conclusions:

• IFABP's portal domain plays a significant role in its interaction with and penetration into cell membranes.
• Lipid composition critically influences IFABP's membrane binding and orientation.
• Findings provide insights into the mechanisms of ligand transfer and FABP family specificity.