Where academic tradition
meets the exciting future

You are here: TUCS > PUBLICATIONS > Publication Search > Three-Dimensional cryoEM Recon...

Three-Dimensional cryoEM Reconstruction of Native LDL Particles to 16A° Resolution at Physiological Body Temperature

Vibhor Kumar, Sarah J Butcher, Katariina Öörni, Peter Engelhardt, Jukka Heikkonen, Kimmo Kaski, Mika Ala-Korpela, Petri T Kovanen, Three-Dimensional cryoEM Reconstruction of Native LDL Particles to 16A° Resolution at Physiological Body Temperature . PloS ONE 6(5), 1–11, 2011.

Abstract:

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 (37uC).

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 6uC and 37uC 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 6uC than at 37uC, 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 6uC, but not at 37uC. At 37uC we were able to highlight features in the LDL particles that are not clearly separable in 3D maps at 6uC. 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.

BibTeX entry:

@ARTICLE{jKuBuOEnHeKaAlKo11a,
  title = {Three-Dimensional cryoEM Reconstruction of Native LDL Particles to 16A° Resolution at Physiological Body Temperature },
  author = {Kumar, Vibhor and Butcher, Sarah J and Öörni, Katariina and Engelhardt, Peter and Heikkonen, Jukka and Kaski, Kimmo and Ala-Korpela, Mika and Kovanen, Petri T},
  journal = {PloS ONE},
  volume = {6},
  number = {5},
  pages = {1–11},
  year = {2011},
}

Belongs to TUCS Research Unit(s): Algorithmics and Computational Intelligence Group (ACI)

Publication Forum rating of this publication: level 2

Edit publication