High-density lipoprotein (HDL)—known as the “good cholesterol” because it is protective against cardiovascular diseases—is an assembly of lipids and proteins.

HDL forms when two copies of apolipoprotein A-1 (APOA1) remove lipids from cells and generate a disc-like structure, which then matures into spherical circulating HDL. Despite decades of study, understanding of HDL structure and maturation has been elusive.

Jere Segrest, MD, PhD, and colleagues have now used molecular dynamics simulations to reveal structural details of newly formed HDL particles. They supported the proposed structures using chemical cross-linking, molecular modeling, and analysis of a lipid-free crystal structure of APOA1.

The structures, reported in the Proceedings of the National Academy of Sciences, revise previous models of nascent HDL and provide a framework for understanding HDL maturation and function. The structural features they identified likely regulate the size and shapes of HDL and form binding sites for proteins involved in transporting cholesterol and fats out of artery walls.