Cryo-electron microscopy reveals human low density lipoprotein substructure.

: In the present study, we have examined the structure of human low density lipoprotein (LDL) using cryo-electron microscopy. Human LDL particles were analyzed in a vitrified frozen-hydrated condition, without chemical fixation or any form of staining. Hence, the lipoproteins were visualized close to their native state. Contrary to current spherical models, the overall shape of human LDL is indicated to be discoidal. The observed LDL disks have a diameter of 21.4 +/- 1.3 nm and a height of 12.1 +/- 1.1 nm (mean +/- standard deviation). The average volume of LDL particles in cryo-electron microscopic preparations is estimated to be 4352 nm3. This value corresponds well with the LDL volume that has been determined by sedimentation equilibrium studies [4130-4803 nm3; Kahlon et al., 1982. Lipids. 17: 323-330]. Details of LDL ultrastructure, visible as a result of local differences in mass density, are indicated to reflect the distribution of protein within the lipoprotein particle. Thus, apolipoprotein B-100 (apoB) appears to form two ring-shaped structures that are organized around the perimeter of the LDL disk.