Three-dimensional structure of low density lipoproteins by electron cryomicroscopy

Elena V. Orlova, Michael B. Sherman, Wah Chiu, Hiro Mowri, Louis C. Smith, Antonio M. Gotto

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Human low density lipoproteins (LDL) are the major cholesterol carriers in the blood. Elevated concentration of LDL is a major risk factor for atherosclerotic disease. Purified LDL particles appear heterogeneous in images obtained 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 was used for three-dimensional reconstruction. In contrast to the general belief that below the lipid phase-transition temperature (30°C) LDL are quasi-spherical microemulsion particles with a radially layered core- shell organization, our three-dimensional map shows that LDL have a well- defined and stable organization. Particles consist of a higher-density outer shell and lower-density inner lamellae-like layers that divide the core into compartments. The outer shell consists of apolipoprotein B-100, phospholipids, and some free cholesterol.

Original languageEnglish (US)
Pages (from-to)8420-8425
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number15
DOIs
StatePublished - Jul 20 1999

Keywords

  • Angular reconstitution
  • Apolipoprotein B-100
  • Lipid
  • Statistical image analysis

ASJC Scopus subject areas

  • General

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