Seipin forms a flexible cage at lipid droplet formation sites

Henning Arlt, Xuewu Sui, Brayden Folger, Carson Adams, Xiao Chen, Roman Remme, Fred A. Hamprecht, Frank DiMaio, Maofu Liao, Joel M. Goodman, Robert V. Farese, Tobias C. Walther

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)194-202
Number of pages9
JournalNature Structural and Molecular Biology
Volume29
Issue number3
DOIs
StatePublished - Mar 2022
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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