title: Immuno-electron cryo-microscopy imaging reveals a looped topology of apoB at the surface of human LDL.
abstract: A single copy of apoB is the sole protein component of human LDL. ApoB is crucial for LDL particle stabilization and is the ligand for LDL receptor, through which cholesterol is delivered to cells. Dysregulation of the pathways of LDL metabolism is well documented in the pathophysiology of atherosclerosis. However, an understanding of the structure of LDL and apoB underlying these biological processes remains limited. In this study, we derived a 22 Å-resolution three-dimensional (3D) density map of LDL using cryo-electron microscopy and image reconstruction, which showed a backbone of high-density regions that encircle the LDL particle. Additional high-density belts complemented this backbone high density to enclose the edge of the LDL particle. Image reconstructions of monoclonal antibody-labeled LDL located six epitopes in five putative domains of apoB in 3D. Epitopes in the LDL receptor binding domain were located on one side of the LDL particle, and epitopes in the N-terminal and C-terminal domains of apoB were in close proximity at the front side of the particle. Such image information revealed a looped topology of apoB on the LDL surface and demonstrated the active role of apoB in maintaining the shape of the LDL particle.
authors: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118.
authors: Yuhang
authors: Y
authors: Liu
authors: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118. Electronic address: atkinson@bu.edu.
authors: David
authors: D
authors: Atkinson
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001055:Apolipoproteins B / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure*; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure*; D016253:Microscopy, Immunoelectron; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure*
chemical_list: D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D011973:Receptors, LDL