Cryo-electron microscopy structure of the lipid droplet-formation protein seipin. Academic Article uri icon

abstract

  • 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 Drosophila melanogaster seipin. The structure reveals a ring-shaped dodecamer with the luminal domain of each monomer resolved at 4.0 . Each luminal domain monomer exhibits two distinctive features: a hydrophobic helix (HH) positioned toward the ER bilayer and a -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.

published proceedings

  • J Cell Biol

author list (cited authors)

  • Sui, X., Arlt, H., Brock, K. P., Lai, Z. W., DiMaio, F., Marks, D. S., ... Walther, T. C.

complete list of authors

  • Sui, Xuewu||Arlt, Henning||Brock, Kelly P||Lai, Zon Weng||DiMaio, Frank||Marks, Debora S||Liao, Maofu||Farese, Robert V||Walther, Tobias C

publication date

  • December 2018