Human SEIPIN Binds Anionic Phospholipids

Renhong Yan, Hongwu Qian, Ivan Lukmantara, Mingming Gao, Ximing Du, Nieng Yan, Hongyuan Yang

Research output: Contribution to journalArticle

43 Scopus citations

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. SEIPIN is an evolutionarily conserved protein that regulates both adipocyte development and the biogenesis of lipid droplets. Yan et al. report the structure of the lumenal domain of human SEIPIN, which exists as an undecamer. The oligomerization state of SEIPIN is critical for its function, and SEIPIN can bind anionic phospholipids.

Original languageEnglish (US)
Pages (from-to)248-256.e4
JournalDevelopmental cell
Volume47
Issue number2
DOIs
StatePublished - Oct 22 2018

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Keywords

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

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  • Cite this

    Yan, R., Qian, H., Lukmantara, I., Gao, M., Du, X., Yan, N., & Yang, H. (2018). Human SEIPIN Binds Anionic Phospholipids. Developmental cell, 47(2), 248-256.e4. https://doi.org/10.1016/j.devcel.2018.09.010