Structure and intermolecular interactions in spheroidal high-density lipoprotein subpopulations

Area of Science:

• Biochemistry
• Structural Biology
• Cardiovascular Science

Background:

• High-density lipoproteins (HDL) are essential for lipid transport and cardiovascular protection.
• HDL exists as distinct subpopulations (HDL3c, HDL3b, HDL3a, HDL2a, HDL2b) with varying sizes, compositions, and functions.

Purpose of the Study:

• To develop and characterize molecular models of five major HDL subpopulations.
• To investigate the structural and compositional differences influencing HDL functionality.

Main Methods:

• Utilized coarse-grained molecular dynamics simulations.
• Developed representative molecular models of HDL subpopulations with multiple apolipoprotein A-I (apoA-I) copies.
• Analyzed particle size, morphology, and molecular interactions.

Main Results:

• HDL models accurately reflected experimental size, morphology, and composition.
• Larger HDL particles showed increased core lipid mixing and defined surface/core separation.
• Specific interactions of cholesterol and triglycerides with apoA-I were identified across subpopulations.
• ApoA-I arrangements varied, but intermolecular contacts were largely maintained.

Conclusions:

• HDL subpopulations exhibit distinct structural and dynamic properties based on size and composition.
• These differences are critical for their varied biological functionalities in lipid metabolism and cardiovascular health.