@article{4063,
  keywords = {Humans, Membrane Proteins, Mutation, Protein Interaction Domains and Motifs, Cryoelectron Microscopy, Hydroxycholesterols, Intracellular Signaling Peptides and Proteins},
  author = {Renhong Yan and Pingping Cao and Wenqi Song and Hongwu Qian and Ximing Du and Hudson Coates and Xin Zhao and Yaning Li and Shuai Gao and Xin Gong and Ximing Liu and Jianhua Sui and Jianlin Lei and Hongyuan Yang and Andrew Brown and Qiang Zhou and Chuangye Yan and Nieng Yan},
  title = {A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.},
  abstract = { <p>The sterol regulatory element-binding protein (SREBP) pathway controls cellular homeostasis of sterols. The key players in this pathway, Scap and Insig-1 and -2, are membrane-embedded sterol sensors. The 25-hydroxycholesterol (25HC)-dependent association of Scap and Insig acts as the master switch for the SREBP pathway. Here, we present cryo-electron microscopy analysis of the human Scap and Insig-2 complex in the presence of 25HC, with the transmembrane (TM) domains determined at an average resolution of 3.7 angstrom. The sterol-sensing domain in Scap and all six TMs in Insig-2 were resolved. A 25HC molecule is sandwiched between the S4 to S6 segments in Scap and TMs 3 and 4 in Insig-2 in the luminal leaflet of the membrane. Unwinding of the middle of the Scap-S4 segment is crucial for 25HC binding and Insig association.</p> },
  year = {2021},
  journal = {Science},
  volume = {371},
  month = {2021 Mar 05},
  issn = {1095-9203},
  doi = {10.1126/science.abb2224},
  language = {eng},
}