LDL and apoB
Cryo-electron tomography reveals a polyhedral, not spherical, 3D structure for VLDL particles (J Lipid Res 2016)
Original title: Polyhedral 3D structure of human plasma very low density lipoproteins by individual particle cryo-electron tomography1
Using cryo-electron microscopy and individual-particle electron tomography, researchers visualized the 3D structure of individual human VLDL particles for the first time and found an unexpected polyhedral shape rather than the generally accepted spherical emulsion-like model. Compared with HDL, VLDL surface lipids showed smaller curvature, which may reduce surface hydrophobicity and explain the lower binding affinity of the hydrophobic distal end of the N-terminal beta-barrel domain of cholesteryl ester transfer protein (CETP) to VLDL relative to HDL. This directional difference in CETP binding to HDL versus VLDL may explain how CETP transfers triglycerides and cholesteryl esters between these particle classes, offering new structural insight into the role of VLDL in atherogenesis.
Original abstract
Human VLDLs assembled in the liver and secreted into the circulation supply energy to peripheral tissues. VLDL lipolysis yields atherogenic LDLs and VLDL remnants that strongly correlate with CVD. Although the composition of VLDL particles has been well-characterized, their 3D structure is elusive because of their variations in size, heterogeneity in composition, structural flexibility, and mobility in solution. Here, we employed cryo-electron microscopy and individual-particle electron tomography to study the 3D structure of individual VLDL particles (without averaging) at both below and above their lipid phase transition temperatures. The 3D reconstructions of VLDL and VLDL bound to antibodies revealed an unexpected polyhedral shape, in contrast to the generally accepted model of a spherical emulsion-like particle. The smaller curvature of surface lipids compared with HDL may also reduce surface hydrophobicity, resulting in lower binding affinity to the hydrophobic distal end of the N-terminal β-barrel domain of cholesteryl ester transfer protein (CETP) compared with HDL. The directional binding of CETP to HDL and VLDL may explain the function of CETP in transferring TGs and cholesteryl esters between these particles. This first visualization of the 3D structure of VLDL could improve our understanding of the role of VLDL in atherogenesis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.