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TitleA structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
Journal, issue, pagesScience, Vol. 371, Issue 6533, Year 2021
Publish dateMar 5, 2021
AuthorsRenhong Yan / Pingping Cao / Wenqi Song / Hongwu Qian / Ximing Du / Hudson W Coates / Xin Zhao / Yaning Li / Shuai Gao / Xin Gong / Ximing Liu / Jianhua Sui / Jianlin Lei / Hongyuan Yang / Andrew J Brown / Qiang Zhou / Chuangye Yan / Nieng Yan /
PubMed AbstractThe 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 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.
External linksScience / PubMed:33446483
MethodsEM (single particle)
Resolution3.7 Å
Structure data

30074

6m49

EMDB-30074, PDB-6m49:
cryo-EM structure of Scap/Insig complex in the present of 25-hydroxyl cholesterol.
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

ChemComp-HC3:
25-HYDROXYCHOLESTEROL

Source
  • homo sapiens (human)
Keywords25-hydroxycholesterol / Cryoelectron Microscopy / Humans / Hydroxycholesterols / INSIG2 protein, human / Intracellular Signaling Peptides and Proteins / Membrane Proteins / Mutation / Protein Interaction Domains and Motifs / SREBP cleavage-activating protein / MEMBRANE PROTEIN / Scap / Insig / cholesterol / sterol sensing / SREBP

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