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

Show full item record



Permalink

http://hdl.handle.net/10138/165655

Citation

Kumar , V , Butcher , S J , Öörni , K , Engelhardt , P , Heikkonen , J , Kaski , K , Ala-Korpela , M & Kovanen , P T 2011 , ' Three-Dimensional cryoEM Reconstruction of Native LDL Particles to 16 angstrom Resolution at Physiological Body Temperature ' , PLoS One , vol. 6 , no. 5 , pp. e18841 . https://doi.org/10.1371/journal.pone.0018841

Title: Three-Dimensional cryoEM Reconstruction of Native LDL Particles to 16 angstrom Resolution at Physiological Body Temperature
Author: Kumar, Vibhor; Butcher, Sarah J.; Öörni, Katariina; Engelhardt, Peter; Heikkonen, Jukka; Kaski, Kimmo; Ala-Korpela, Mika; Kovanen, Petri T.
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Wihuri Research Institute
University of Helsinki, Haartman Institute (-2014)
University of Helsinki, Clinicum
Date: 2011
Language: eng
Number of pages: 11
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/165655
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 (37°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°C and 37°C resulted in reconstructions at ~16 Å 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°C than at 37°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°C, but not at 37°C. At 37°C we were able to highlight features in the LDL particles that are not clearly separable in 3D maps at 6°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.
Subject: LOW-DENSITY-LIPOPROTEIN
CRYOELECTRON MICROSCOPY
APOLIPOPROTEIN-B
STATISTICAL-ANALYSIS
SERUM-LIPOPROTEINS
TRANSFER PROTEIN
MODEL
LIPOVITELLIN
IMAGES
B-100
1182 Biochemistry, cell and molecular biology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
journal.pone.0018841.PDF 4.076Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record