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Dev Cell. 2018 Oct 22;47(2):248-256.e4. doi: 10.1016/j.devcel.2018.09.010. Epub 2018 Oct 4.

Human SEIPIN Binds Anionic Phospholipids.

Author information

1
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.
2
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. Electronic address: hongwuq@princeton.edu.
3
School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW 2052, Australia.
4
Laboratory of Lipid Metabolism, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
5
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; Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA. Electronic address: nyan@princeton.edu.
6
School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: h.rob.yang@unsw.edu.au.

Abstract

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.

KEYWORDS:

BSCL2; GPAT; PI(3)P; SEIPIN; adipogenesis; adipose tissue; congenital generalize lipodystrophy; lipid droplets; phosphatidic acid; undecamer

PMID:
30293840
DOI:
10.1016/j.devcel.2018.09.010
[Indexed for MEDLINE]

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