Journal
PLOS ONE
Volume 6, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0018841
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Funding
- Academy of Finland [1129684]
- Finnish Cardiovascular Research Foundation
- Sigrid Juselius Foundation
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Background: Low-density lipoprotein (LDL) particles, the major carriers of cholesterol in the human circulation, have a key role in cholesterol physiology and in the development of atherosclerosis. The most prominent structural components in LDL are the core-forming cholesteryl esters (CE) and the particle-encircling single copy of a huge, non-exchangeable protein, the apolipoprotein B-100 (apoB-100). The shape of native LDL particles and the conformation of native apoB-100 on the particles remain incompletely characterized at the physiological human body temperature (37 degrees C). Methodology/Principal Findings: To study native LDL particles, we applied cryo-electron microscopy to calculate 3D reconstructions of LDL particles in their hydrated state. Images of the particles vitrified at 6 degrees C and 37 degrees C resulted in reconstructions at,16 A resolution at both temperatures. 3D variance map analysis revealed rigid and flexible domains of lipids and apoB-100 at both temperatures. The reconstructions showed less variability at 6 degrees C than at 37 degrees C, which reflected increased order of the core CE molecules, rather than decreased mobility of the apoB-100. Compact molecular packing of the core and order in a lipid-binding domain of apoB-100 were observed at 6 degrees C, but not at 37 degrees C. At 37 degrees C we were able to highlight features in the LDL particles that are not clearly separable in 3D maps at 6 degrees C. Segmentation of apoB-100 density, fitting of lipovitellin X-ray structure, and antibody mapping, jointly revealed the approximate locations of the individual domains of apoB-100 on the surface of native LDL particles. Conclusions/Significance: Our study provides molecular background for further understanding of the link between structure and function of native LDL particles at physiological body temperature.
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