Cryo-EM structure of Scap/Insig complex in the present of digitonin.Cryo-EM structure of Scap/Insig complex in the present of digitonin.

Structural highlights

7etw is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 4.1Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

INSI2_HUMAN Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Seems to regulate the ubiquitin-mediated proteasomal degradation of HMGCR.[1] [2]

References

  1. Yabe D, Brown MS, Goldstein JL. Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12753-8. Epub 2002 Sep 19. PMID:12242332 doi:10.1073/pnas.162488899
  2. Gong Y, Lee JN, Brown MS, Goldstein JL, Ye J. Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol homeostasis. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6154-9. Epub 2006 Apr 10. PMID:16606821 doi:0601923103

7etw, resolution 4.10Å

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