Cryo-electron Microscopy Structure of the Lipid Droplet-formation Protein Seipin

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2018 Oct 18

PMID 30327422

Citations 80

Authors

Xuewu Sui

Henning Arlt

Kelly P Brock

Zon Weng Lai

Frank DiMaio

Debora S Marks

Maofu Liao

Robert V Farese Jr

Tobias C Walther

Affiliations

Soon will be listed here.

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.

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