Seipin traps triacylglycerols to facilitate their nanoscale clustering in the endoplasmic reticulum membrane

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Prasanna , X , Salo , V T , Li , S , Ven , K , Vihinen , H , Jokitalo , E , Vattulainen , I & Ikonen , E 2021 , ' Seipin traps triacylglycerols to facilitate their nanoscale clustering in the endoplasmic reticulum membrane ' , PLoS Biology , vol. 19 , no. 1 , 3000998 . https://doi.org/10.1371/journal.pbio.3000998

Title: Seipin traps triacylglycerols to facilitate their nanoscale clustering in the endoplasmic reticulum membrane
Author: Prasanna, Xavier; Salo, Veijo Tuomas; Li, Shiqian; Ven, Katharina; Vihinen, Helena; Jokitalo, Eija; Vattulainen, Ilpo; Ikonen, Elina
Other contributor: University of Helsinki, Materials Physics
University of Helsinki, Department of Anatomy
University of Helsinki, Department of Anatomy
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Department of Physics
University of Helsinki, Lipid Trafficking Lab




Date: 2021-01-22
Language: eng
Number of pages: 24
Belongs to series: PLoS Biology
ISSN: 1544-9173
DOI: https://doi.org/10.1371/journal.pbio.3000998
URI: http://hdl.handle.net/10138/328277
Abstract: Seipin is a disk-like oligomeric endoplasmic reticulum (ER) protein important for lipid droplet (LD) biogenesis and triacylglycerol (TAG) delivery to growing LDs. Here we show through biomolecular simulations bridged to experiments that seipin can trap TAGs in the ER bilayer via the luminal hydrophobic helices of the protomers delineating the inner opening of the seipin disk. This promotes the nanoscale sequestration of TAGs at a concentration that by itself is insufficient to induce TAG clustering in a lipid membrane. We identify Ser166 in the alpha 3 helix as a favored TAG occupancy site and show that mutating it compromises the ability of seipin complexes to sequester TAG in silico and to promote TAG transfer to LDs in cells. While the S166D-seipin mutant colocalizes poorly with promethin, the association of nascent wild-type seipin complexes with promethin is promoted by TAGs. Together, these results suggest that seipin traps TAGs via its luminal hydrophobic helices, serving as a catalyst for seeding the TAG cluster from dissolved monomers inside the seipin ring, thereby generating a favorable promethin binding interface.
Subject: ASYMMETRY
BINDING
CONTACTS
FORCE-FIELD
LIPID DROPLET BIOGENESIS
LIPODYSTROPHY
PROTEINS
STRESS
VALIDATION
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
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