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Title: Polyhedral 3D structure of human plasma very low density lipoproteins by individual particle cryo-electron tomography

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:
 [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Foundry
  2. Children's Hospital Oakland Research Inst., Oakland, CA (United States). Atherosclerosis Research
Publication Date:
Grant/Contract Number:
AC02-05CH11231; R01GM104427; R01HL115153
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
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; apolipoprotein B; antibodies; electron microscopy; three-dimensional
OSTI Identifier:
1377508