Three-dimensional structure of low density lipoproteins by electron cryomicroscopy

Human low density lipoproteins (LDL) are the major cholesterol carriers in the blood. Elevated concentration of LDL is a major risk factor for atheros clerotic disease. Purified LDL particles appear heterogeneous in images obt ained with a 400-kV electron cryomicroscope. Using multivariate statistical and cluster analyses, an ensemble of randomly oriented particle images has been subdivided into homogeneous subpopulations, and the largest subset wa s used for three-dimensional reconstruction, In contrast to the general bel ief that below the lipid phase-transition temperature (30 degrees C) LDL ar e quasi-spherical microemulsion particles with a radially layered core-shel l organization, our three-dimensional map shows that LDL have a well-define d and stable organization, Particles consist of a higher-density outer shel l and lower-density inner lamellae-like layers that divide the core into co mpartments. The outer shell consists of apolipoprotein B-100, phospholipids , and some free cholesterol.