Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
Dev Cell. 2018 Oct 22;47(2):248-256.e4. doi: 10.1016/j.devcel.2018.09.010. Epub 2018 Oct 4.
The biogenesis of lipid droplets (LDs) and the development of adipocytes are two key aspects of mammalian fat storage. SEIPIN, an integral membrane protein of the endoplasmic reticulum (ER), plays a critical role in both LD formation and adipogenesis. The molecular function of SEIPIN, however, has yet to be elucidated. Here, we report the cryogenic electron microscopy structure of human SEIPIN at 3.8 Å resolution. SEIPIN exists as an undecamer, and this oligomerization state is critical for its physiological function. The evolutionarily conserved lumenal domain of SEIPIN forms an eight-stranded β sandwich fold. Both full-length SEIPIN and its lumenal domain can bind anionic phospholipids including phosphatidic acid. Our results suggest that SEIPIN forms a scaffold that helps maintain phospholipid homeostasis and surface tension of the ER.
脂滴（LDs）的生物发生和脂肪细胞的发育是哺乳动物脂肪储存的两个关键方面。内质网（ER）的整合膜蛋白 SEIPIN 在 LD 形成和脂肪生成中都起着关键作用。然而，SEIPIN 的分子功能尚不清楚。在这里，我们报道了分辨率为 3.8Å 的人 SEIPIN 的低温电子显微镜结构。SEIPIN 以十一聚体的形式存在，这种寡聚状态对于其生理功能至关重要。SEIPIN 进化上保守的腔内腔域形成一个八链β三明治折叠。全长 SEIPIN 及其腔内腔域都可以结合阴离子磷脂，包括磷酸脂。我们的结果表明，SEIPIN 形成了一个支架，有助于维持 ER 中的磷脂稳态和表面张力。
