Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.

<h4>Background</h4>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 es...

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Autores principales:	Vibhor Kumar, Sarah J Butcher, Katariina Öörni, Peter Engelhardt, Jukka Heikkonen, Kimmo Kaski, Mika Ala-Korpela, Petri T Kovanen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3bc145db1cc642a99f5f82be6aca3aa0
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spelling	oai:doaj.org-article:3bc145db1cc642a99f5f82be6aca3aa02021-11-18T06:54:15ZThree-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.1932-620310.1371/journal.pone.0018841https://doaj.org/article/3bc145db1cc642a99f5f82be6aca3aa02011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21573056/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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).<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>Our study provides molecular background for further understanding of the link between structure and function of native LDL particles at physiological body temperature.Vibhor KumarSarah J ButcherKatariina ÖörniPeter EngelhardtJukka HeikkonenKimmo KaskiMika Ala-KorpelaPetri T KovanenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e18841 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 16Å resolution at physiological body temperature.
description	<h4>Background</h4>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).<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>Our study provides molecular background for further understanding of the link between structure and function of native LDL particles at physiological body temperature.
format	article
author	Vibhor Kumar Sarah J Butcher Katariina Öörni Peter Engelhardt Jukka Heikkonen Kimmo Kaski Mika Ala-Korpela Petri T Kovanen
author_facet	Vibhor Kumar Sarah J Butcher Katariina Öörni Peter Engelhardt Jukka Heikkonen Kimmo Kaski Mika Ala-Korpela Petri T Kovanen
author_sort	Vibhor Kumar
title	Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.
title_short	Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.
title_full	Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.
title_fullStr	Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.
title_full_unstemmed	Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.
title_sort	three-dimensional cryoem reconstruction of native ldl particles to 16å resolution at physiological body temperature.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3bc145db1cc642a99f5f82be6aca3aa0
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Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.

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