@article{459bf5bd7d824c3abbb9353aa7eab2a3,
title = "Seipin forms a flexible cage at lipid droplet formation sites",
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.",
author = "Henning Arlt and Xuewu Sui and Brayden Folger and Carson Adams and Xiao Chen and Roman Remme and Hamprecht, {Fred A.} and Frank DiMaio and Maofu Liao and Goodman, {Joel M.} and Farese, {Robert V.} and Walther, {Tobias C.}",
note = "Funding Information: We thank S. Kim and G. Voth (Department of Chemistry, University of Chicago) for critical discussions, K. Brock and D. Marks (HMS, Systems Biology) for advice on evolutionary coupling analyses and C.-W. Wang (Institute of Plant and Microbial Biology, Academia Sinica, Taipei City) for kindly sharing the Ldb16 antibody. We thank D. Moazed (HMS, Cell Biology) for sharing of equipment, S. Sterling, R. Walsh and Z. Li at the Harvard cryo-EM center for EM data collection, J. Reus, N. Paul, A. Gan and D. Chukwuma for generating and phenotyping several yeast strains and G. Howard for editorial assistance. This work was supported by National Institutes of Health (NIH) grant no. R01GM124348 (to R.V.F.), NIH grant no. R01GM084210 (to J.M.G.), a German Research Foundation (DFG) fellowship no. AR1164/1-1 (to H.A.) and an American Heart Association postdoctoral fellowship no. 18POST34030308 (to X.S.). T.C.W. is an investigator of the Howard Hughes Medical Institute. Funding Information: We thank S. Kim and G. Voth (Department of Chemistry, University of Chicago) for critical discussions, K. Brock and D. Marks (HMS, Systems Biology) for advice on evolutionary coupling analyses and C.-W. Wang (Institute of Plant and Microbial Biology, Academia Sinica, Taipei City) for kindly sharing the Ldb16 antibody. We thank D. Moazed (HMS, Cell Biology) for sharing of equipment, S. Sterling, R. Walsh and Z. Li at the Harvard cryo-EM center for EM data collection, J. Reus, N. Paul, A. Gan and D. Chukwuma for generating and phenotyping several yeast strains and G. Howard for editorial assistance. This work was supported by National Institutes of Health (NIH) grant no. R01GM124348 (to R.V.F.), NIH grant no. R01GM084210 (to J.M.G.), a German Research Foundation (DFG) fellowship no. AR1164/1-1 (to H.A.) and an American Heart Association postdoctoral fellowship no. 18POST34030308 (to X.S.). T.C.W. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = mar,
doi = "10.1038/s41594-021-00718-y",
language = "English (US)",
volume = "29",
pages = "194--202",
journal = "Nature Structural Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "3",
}