Seipin forms a flexible cage at lipid droplet formation sites

Nat Struct Mol Biol. 2022 Mar;29(3):194-202. doi: 10.1038/s41594-021-00718-y. Epub 2022 Feb 24.


Lipid droplets (LDs) form in the endoplasmic reticulum by phase separation of neutral lipids. This process is facilitated by the seipin protein complex, which consists of a ring of seipin monomers, with a yet unclear function. Here, we report a structure of S. cerevisiae seipin based on cryogenic-electron microscopy and structural modeling data. Seipin forms a decameric, cage-like structure with the lumenal domains forming a stable ring at the cage floor and transmembrane segments forming the cage sides and top. The transmembrane segments interact with adjacent monomers in two distinct, alternating conformations. These conformations result from changes in switch regions, located between the lumenal domains and the transmembrane segments, that are required for seipin function. Our data indicate a model for LD formation in which a closed seipin cage enables triacylglycerol phase separation and subsequently switches to an open conformation to allow LD growth and budding.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoplasmic Reticulum / metabolism
  • GTP-Binding Protein gamma Subunits* / chemistry
  • Lipid Droplets* / chemistry
  • Lipid Droplets* / metabolism
  • Lipid Metabolism
  • Membrane Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism


  • GTP-Binding Protein gamma Subunits
  • Membrane Proteins