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

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....

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Autores principales: Sui, Xuewu, Arlt, Henning, Brock, Kelly P., Lai, Zon Weng, DiMaio, Frank, Marks, Debora S., Liao, Maofu, Farese, Robert V., Walther, Tobias C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279392/
https://www.ncbi.nlm.nih.gov/pubmed/30327422
http://dx.doi.org/10.1083/jcb.201809067
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author Sui, Xuewu
Arlt, Henning
Brock, Kelly P.
Lai, Zon Weng
DiMaio, Frank
Marks, Debora S.
Liao, Maofu
Farese, Robert V.
Walther, Tobias C.
author_facet Sui, Xuewu
Arlt, Henning
Brock, Kelly P.
Lai, Zon Weng
DiMaio, Frank
Marks, Debora S.
Liao, Maofu
Farese, Robert V.
Walther, Tobias C.
author_sort Sui, Xuewu
collection PubMed
description 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.
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spelling pubmed-62793922019-06-03 Cryo–electron microscopy structure of the lipid droplet–formation protein seipin Sui, Xuewu Arlt, Henning Brock, Kelly P. Lai, Zon Weng DiMaio, Frank Marks, Debora S. Liao, Maofu Farese, Robert V. Walther, Tobias C. J Cell Biol Research Articles 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. Rockefeller University Press 2018-12-03 /pmc/articles/PMC6279392/ /pubmed/30327422 http://dx.doi.org/10.1083/jcb.201809067 Text en © 2018 Sui et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Sui, Xuewu
Arlt, Henning
Brock, Kelly P.
Lai, Zon Weng
DiMaio, Frank
Marks, Debora S.
Liao, Maofu
Farese, Robert V.
Walther, Tobias C.
Cryo–electron microscopy structure of the lipid droplet–formation protein seipin
title Cryo–electron microscopy structure of the lipid droplet–formation protein seipin
title_full Cryo–electron microscopy structure of the lipid droplet–formation protein seipin
title_fullStr Cryo–electron microscopy structure of the lipid droplet–formation protein seipin
title_full_unstemmed Cryo–electron microscopy structure of the lipid droplet–formation protein seipin
title_short Cryo–electron microscopy structure of the lipid droplet–formation protein seipin
title_sort cryo–electron microscopy structure of the lipid droplet–formation protein seipin
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279392/
https://www.ncbi.nlm.nih.gov/pubmed/30327422
http://dx.doi.org/10.1083/jcb.201809067
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