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PreprintCited by 107Lipid metabolism and biosynthesisProtein Structure and DynamicsLipid Membrane Structure and Behavior

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Seipin forms a flexible cage at lipid droplet formation sites

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Arlt, Henning, Sui, Xuewu, Folger, Brayden, Adams, Carson, Chen, Xiao, Remme, Roman, Hamprecht, Fred A., DiMaio, Frank, Liao, Maofu, Goodman, Joel M., Farese, Robert V., Walther, Tobias C.·2021·Nature Structural & Molecular Biology
DOI 10.1101/2021.08.05.455270PMC PMC8930772

Preprint — published as 10.1038/s41594-021-00718-y · Paper page

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Abstract

SUMMARY: 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 yet unclear function. Here, we report a structure of yeast seipin based on cryo-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 suggest a model for LD formation in which a closed seipin cage enables TG phase separation and subsequently switches to an open conformation to allow LD growth and budding.

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Metadata

Authors
Arlt, H., Sui, X., Folger, B., Adams, C., Chen, X., Remme, R., Hamprecht, F. A., DiMaio, F., Liao, M., Goodman, J. M., Farese, R. V., & Walther, T. C.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Harvard University (US)
  • The University of Texas Southwestern Medical Center (US)
  • University of Washington (US)
  • Heidelberg University (DE)
  • Broad Institute (US)
Corresponding author
  • Goodman, Joel M.
  • Farese, Robert V.
  • Walther, Tobias C.
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
openRxiv
Published
2021-08-06
Volume
29
Issue
3
Pages
194-202
ISSN
1545-9985 (ISSN-L)
DOI
10.1101/2021.08.05.455270
PMC
PMC8930772
OpenAlex
W4220940324
Cited by
107
References
1
Citations by year
2026: 18 · 2025: 34 · 2024: 26 · 2023: 15 · 2022: 14
FWCI
9.38
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • American Heart Association (18POST34030308)
  • Deutsche Forschungsgemeinschaft (AR1164/1-1)
  • Academia Sinica
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM124348, R01GM084210, R01GM123089)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
seipin, lipid droplet formation, phase separation, triglycerides, endoplasmic reticulum, switch regions, protein structure
MeSH terms
Endoplasmic Reticulum, Membrane Proteins, Saccharomyces cerevisiae, GTP-Binding Protein gamma Subunits, Lipid Metabolism, Lipid Droplets

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