Polyhedral 3D structure of human plasma very low density lipoproteins by individual particle cryo-electron tomography
Abstract
Human VLDLs assembled in the liver and secreted into the circulation supply energy to peripheral tissues. VLDL lipolysis yields atherogenic LDLs and VLDL remnants that strongly correlate with CVD. Although the composition of VLDL particles has been well-characterized, their 3D structure is elusive because of their variations in size, heterogeneity in composition, structural flexibility, and mobility in solution. Here, we employed cryo-electron microscopy and individual-particle electron tomography to study the 3D structure of individual VLDL particles (without averaging) at both below and above their lipid phase transition temperatures. The 3D reconstructions of VLDL and VLDL bound to antibodies revealed an unexpected polyhedral shape, in contrast to the generally accepted model of a spherical emulsion-like particle. The smaller curvature of surface lipids compared with HDL may also reduce surface hydrophobicity, resulting in lower binding affinity to the hydrophobic distal end of the N-terminal β-barrel domain of cholesteryl ester transfer protein (CETP) compared with HDL. The directional binding of CETP to HDL and VLDL may explain the function of CETP in transferring TGs and cholesteryl esters between these particles. This first visualization of the 3D structure of VLDL could improve our understanding of the role of VLDL in atherogenesis.
- Authors:
-
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Foundry
- Children's Hospital Oakland Research Inst., Oakland, CA (United States). Atherosclerosis Research
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)
- OSTI Identifier:
- 1377508
- Grant/Contract Number:
- AC02-05CH11231; R01GM104427; R01HL115153
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Lipid Research
- Additional Journal Information:
- Journal Volume: 57; Journal Issue: 10; Journal ID: ISSN 0022-2275
- Publisher:
- American Society for Biochemistry and Molecular Biology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; apolipoprotein B; antibodies; electron microscopy; three-dimensional
Citation Formats
Yu, Yadong, Kuang, Yu-Lin, Lei, Dongsheng, Zhai, Xiaobo, Zhang, Meng, Krauss, Ronald M., and Ren, Gang. Polyhedral 3D structure of human plasma very low density lipoproteins by individual particle cryo-electron tomography. United States: N. p., 2016.
Web. doi:10.1194/jlr.M070375.
Yu, Yadong, Kuang, Yu-Lin, Lei, Dongsheng, Zhai, Xiaobo, Zhang, Meng, Krauss, Ronald M., & Ren, Gang. Polyhedral 3D structure of human plasma very low density lipoproteins by individual particle cryo-electron tomography. United States. https://doi.org/10.1194/jlr.M070375
Yu, Yadong, Kuang, Yu-Lin, Lei, Dongsheng, Zhai, Xiaobo, Zhang, Meng, Krauss, Ronald M., and Ren, Gang. Thu .
"Polyhedral 3D structure of human plasma very low density lipoproteins by individual particle cryo-electron tomography". United States. https://doi.org/10.1194/jlr.M070375. https://www.osti.gov/servlets/purl/1377508.
@article{osti_1377508,
title = {Polyhedral 3D structure of human plasma very low density lipoproteins by individual particle cryo-electron tomography},
author = {Yu, Yadong and Kuang, Yu-Lin and Lei, Dongsheng and Zhai, Xiaobo and Zhang, Meng and Krauss, Ronald M. and Ren, Gang},
abstractNote = {Human VLDLs assembled in the liver and secreted into the circulation supply energy to peripheral tissues. VLDL lipolysis yields atherogenic LDLs and VLDL remnants that strongly correlate with CVD. Although the composition of VLDL particles has been well-characterized, their 3D structure is elusive because of their variations in size, heterogeneity in composition, structural flexibility, and mobility in solution. Here, we employed cryo-electron microscopy and individual-particle electron tomography to study the 3D structure of individual VLDL particles (without averaging) at both below and above their lipid phase transition temperatures. The 3D reconstructions of VLDL and VLDL bound to antibodies revealed an unexpected polyhedral shape, in contrast to the generally accepted model of a spherical emulsion-like particle. The smaller curvature of surface lipids compared with HDL may also reduce surface hydrophobicity, resulting in lower binding affinity to the hydrophobic distal end of the N-terminal β-barrel domain of cholesteryl ester transfer protein (CETP) compared with HDL. The directional binding of CETP to HDL and VLDL may explain the function of CETP in transferring TGs and cholesteryl esters between these particles. This first visualization of the 3D structure of VLDL could improve our understanding of the role of VLDL in atherogenesis.},
doi = {10.1194/jlr.M070375},
journal = {Journal of Lipid Research},
number = 10,
volume = 57,
place = {United States},
year = {Thu Aug 18 00:00:00 EDT 2016},
month = {Thu Aug 18 00:00:00 EDT 2016}
}
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