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