CETP and exchangeable apoproteins: common features in lipid binding activity

Area of Science:

• Biochemistry
• Molecular Biology
• Lipid Metabolism

Background:

• Cholesteryl ester transfer protein (CETP) plays a crucial role in lipoprotein metabolism.
• Understanding the lipid-binding domain of CETP is essential for elucidating its function in lipid transport.
• Apoproteins share structural similarities and functional roles in lipid binding.

Purpose of the Study:

• To define the active domain for lipid binding in CETP.
• To compare the physicochemical properties of CETP with those of various apoproteins (apoAI, apoAII, apoCI, CII, CIII, apoE).
• To investigate the structural basis of lipid-protein interactions.

Main Methods:

• Analysis of fundamental physicochemical properties: hydrophobic moment, protein active surface, and helix amphipathicity.
• Comparative analysis with reported properties of exchangeable apoproteins.
• Identification of specific amino acid array patterns (i, i+3 and i, i+4) in lipid-binding regions.

Main Results:

• CETP exhibits an active surface slightly lower than that of exchangeable apoproteins.
• Specific arrays (i, i+3 and i, i+4) found in apoprotein lipid-binding regions were also identified in CETP.
• Seven such arrays in CETP's amphipathic alpha-helices are proposed to contribute to lipid binding via alpha-helix stability.

Conclusions:

• CETP's lipid-binding activity is associated with its amphipathic alpha-helices and specific amino acid arrays.
• A conformational specificity, possibly involving a redundant stereochemical code, is proposed to operate for lipid binding in both CETP and apoproteins.
• The findings provide insights into the molecular mechanisms of lipid transfer and transport.