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

J Cell Biol
Authors
Keywords
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 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.

Year of Publication
2018
Journal
J Cell Biol
Volume
217
Issue
12
Pages
4080-4091
Date Published
2018 Dec 03
ISSN
1540-8140
DOI
10.1083/jcb.201809067
PubMed ID
30327422
PubMed Central ID
PMC6279392
Links
Grant list
R01 GM123089 / GM / NIGMS NIH HHS / United States
R01 GM124348 / GM / NIGMS NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States