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Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex

  1. Author:
    Klug, Yoel A.
    Deme, Justin C.
    Corey, Robin A.
    Renne, Mike F.
    Stansfeld, Phillip J.
    Lea, Susan M.
    Carvalho, Pedro

  2. Author Address

    Univ Oxford, Sir William Dunn Sch Pathol, Oxford, England.NCI, Ctr Struct Biol, Ctr Canc Res, Frederick, MD 21701 USA.Univ Oxford, Dept Biochem, Oxford, England.Univ Warwick, Sch Life Sci, Coventry, W Midlands, England.Univ Warwick, Dept Chem, Coventry, W Midlands, England.
    1. Year: 2021
    2. Date: Oct 8
  2. Journal: Nature Communications
  3. Nature Portfolio
    1. 12
    2. 1
  5. Type of Article: Article
  6. Article Number: 5892
  7. ISSN: 2041-1723
  1. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41467-021-26162-6
  3. PMID: 34625558
  4. PMCID: PMC8501077
  5. View record in Web of Science®
  6. WOS: 000705238300018

Library Notes

  1. Fiscal Year: FY2021-2022
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