Journal article
Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex
- Abstract:
- Lipid droplets (LDs) are universal lipid storage organelles with a core of neutral lipids, such as triacylglycerols, surrounded by a phospholipid monolayer. This unique architecture is generated during LD biogenesis at endoplasmic reticulum (ER) sites marked by Seipin, a conserved membrane protein mutated in lipodystrophy. Here structural, biochemical and molecular dynamics simulation approaches reveal the mechanism of LD formation by the yeast Seipin Sei1 and its membrane partner Ldb16. We show that Sei1 luminal domain assembles a homooligomeric ring, which, in contrast to other Seipins, is unable to concentrate triacylglycerol. Instead, Sei1 positions Ldb16, which concentrates triacylglycerol within the Sei1 ring through critical hydroxyl residues. Triacylglycerol recruitment to the complex is further promoted by Sei1 transmembrane segments, which also control Ldb16 stability. Thus, we propose that LD assembly by the Sei1/Ldb16 complex, and likely other Seipins, requires sequential triacylglycerol-concentrating steps via distinct elements in the ER membrane and lumen.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.4MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-021-26162-6
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Communications More from this journal
- Volume:
- 12
- Issue:
- 1
- Pages:
- 5892-5892
- Article number:
- 5892
- Publication date:
- 2021-10-08
- Acceptance date:
- 2021-09-21
- DOI:
- EISSN:
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2041-1723
- ISSN:
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2041-1723
- Pmid:
-
34625558
- Language:
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English
- Keywords:
- Pubs id:
-
1201771
- UUID:
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uuid_14c2f0b7-3b27-498a-9317-30449250201c
- Local pid:
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pubs:1201771
- Deposit date:
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2022-04-08
- ARK identifier:
Terms of use
- Copyright holder:
- Klug et al.
- Copyright date:
- 2021
- Rights statement:
- ©2021 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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