National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
1R01GM123089
米国
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
1R01GM124348-01
米国
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
R01GM097194
米国
American Heart Association
18POST34030308
米国
German Research Foundation (DFG)
AR1164/1-1
ドイツ
引用
ジャーナル: J Cell Biol / 年: 2018 タイトル: Cryo-electron microscopy structure of the lipid droplet-formation protein seipin. 著者: Xuewu Sui / Henning Arlt / Kelly P Brock / Zon Weng Lai / Frank DiMaio / Debora S Marks / Maofu Liao / Robert V Farese / Tobias C Walther / 要旨: Metabolic energy is stored in cells primarily as triacylglycerols in lipid droplets (LDs), and LD dysregulation leads to metabolic diseases. The formation of monolayer-bound LDs from the endoplasmic ...Metabolic energy is stored in cells primarily as triacylglycerols in lipid droplets (LDs), and LD dysregulation leads to metabolic diseases. The formation of monolayer-bound LDs from the endoplasmic reticulum (ER) bilayer is poorly understood, but the ER protein seipin is essential to this process. In this study, we report a cryo-electron microscopy structure and functional characterization of seipin. The structure reveals a ring-shaped dodecamer with the luminal domain of each monomer resolved at ∼4.0 Å. Each luminal domain monomer exhibits two distinctive features: a hydrophobic helix (HH) positioned toward the ER bilayer and a β-sandwich domain with structural similarity to lipid-binding proteins. This structure and our functional testing in cells suggest a model in which seipin oligomers initially detect forming LDs in the ER via HHs and subsequently act as membrane anchors to enable lipid transfer and LD growth.