Structural highlights
Function
[BSCL2_DROME] Is a regulator of lipid catabolism essential for adipocyte differentiation. May also be involved in the central regulation of energy homeostasis (By similarity). Necessary for correct lipid storage and lipid droplets maintenance; plays a tissue-autonomous role in controlling lipid storage in adipocytes and in preventing ectopic lipid droplet formation in non-adipose tissues. May participate in phosphatidic acid metabolism and subsequently down-regulate lipogenesis.[UniProtKB:Q9Z2E9][1]
Publication Abstract from PubMed
Metabolic energy is stored in cells primarily as triacylglycerols in lipid droplets (LDs), and LD dysregulation leads to metabolic diseases. The formation of monolayer-bound LDs from the endoplasmic reticulum (ER) bilayer is poorly understood, but the ER protein seipin is essential to this process. In this study, we report a cryo-electron microscopy structure and functional characterization of Drosophila melanogaster seipin. The structure reveals a ring-shaped dodecamer with the luminal domain of each monomer resolved at approximately 4.0 A. Each luminal domain monomer exhibits two distinctive features: a hydrophobic helix (HH) positioned toward the ER bilayer and a beta-sandwich domain with structural similarity to lipid-binding proteins. This structure and our functional testing in cells suggest a model in which seipin oligomers initially detect forming LDs in the ER via HHs and subsequently act as membrane anchors to enable lipid transfer and LD growth.
Cryo-electron microscopy structure of the lipid droplet-formation protein seipin.,Sui X, Arlt H, Brock KP, Lai ZW, DiMaio F, Marks DS, Liao M, Farese RV Jr, Walther TC J Cell Biol. 2018 Oct 16. pii: jcb.201809067. doi: 10.1083/jcb.201809067. PMID:30327422[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tian Y, Bi J, Shui G, Liu Z, Xiang Y, Liu Y, Wenk MR, Yang H, Huang X. Tissue-autonomous function of Drosophila seipin in preventing ectopic lipid droplet formation. PLoS Genet. 2011 Apr;7(4):e1001364. doi: 10.1371/journal.pgen.1001364. Epub 2011 , Apr 14. PMID:21533227 doi:http://dx.doi.org/10.1371/journal.pgen.1001364
- ↑ Sui X, Arlt H, Brock KP, Lai ZW, DiMaio F, Marks DS, Liao M, Farese RV Jr, Walther TC. Cryo-electron microscopy structure of the lipid droplet-formation protein seipin. J Cell Biol. 2018 Oct 16. pii: jcb.201809067. doi: 10.1083/jcb.201809067. PMID:30327422 doi:http://dx.doi.org/10.1083/jcb.201809067
