期刊
PLOS BIOLOGY
卷 19, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.3000998
关键词
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资金
- Academy of Finland Center of Excellence Program [307415]
- Academy of Finland [282192, 312491, 287975]
- Sigrid Juselius Foundation
- Jane and Aatos Erkko Foundation
- HiLIFE Fellow Program
- Doctoral Progamme in Biomedicine
- Finnish Medical Foundation
- Paulo Foundation
- Alfred Kordelin Foundation
- Maud Kuistila Foundation
- Biomedicum Helsinki Foundation
- Emil Aaltonen Foundation
- Academy of Finland (AKA) [287975, 282192, 312491, 287975] Funding Source: Academy of Finland (AKA)
Seipin can trap TAGs in the ER bilayer via its luminal hydrophobic helices, serving as a catalyst for seeding the TAG cluster and generating a favorable promethin binding interface.
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.
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