Cryo-electron microscopy structure of the lipid droplet-formation protein seipin.
Xuewu SuiHenning ArltKelly P BrockZon Weng LaiFrank DiMaioDebora S MarksMaofu LiaoRobert V FareseTobias C WaltherPublished in: The Journal of cell biology (2018)
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.
Keyphrases
- electron microscopy
- endoplasmic reticulum
- induced apoptosis
- drosophila melanogaster
- estrogen receptor
- fatty acid
- cell cycle arrest
- breast cancer cells
- amino acid
- endoplasmic reticulum stress
- cell death
- high throughput
- protein protein
- binding protein
- molecularly imprinted
- mass spectrometry
- dna binding
- electron transfer