Cryo-electron microscopy structure of the lipid droplet-formation protein seipin

J Cell Biol. 2018 Dec 3;217(12):4080-4091. doi: 10.1083/jcb.201809067. Epub 2018 Oct 16.


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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cryoelectron Microscopy
  • Drosophila Proteins* / chemistry
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / ultrastructure
  • GTP-Binding Protein gamma Subunits* / chemistry
  • GTP-Binding Protein gamma Subunits* / genetics
  • GTP-Binding Protein gamma Subunits* / metabolism
  • Lipid Droplets* / metabolism
  • Lipid Droplets* / ultrastructure
  • Models, Biological*
  • Models, Molecular*
  • Protein Domains
  • Structure-Activity Relationship


  • Drosophila Proteins
  • GTP-Binding Protein gamma Subunits

Associated data

  • PDB/2HKA
  • PDB/6MLU