Competition between a transmembrane helix on Scap and a membrane cholesterol regulates Scap-Insig interaction and SREBP activation.

ABSTRACT: Cholesterol homeostasis in mammalian cells relies on the interaction between two endoplasmic reticulum (ER) sterol-sensing membrane proteins, Scap and Insig. Their interaction regulates activation of transcription factors called sterol regulatory element-binding proteins (SREBPs) that control genes for cholesterol biosynthesis and uptake. Previous studies suggested a model where cholesterol sensing by Scap involves communication across the ER membrane between two functional domains, a cholesterol-binding domain on the luminal side and a COPII-binding domain on the cytosolic side. When ER cholesterol is low, Scap binds COPII adapter proteins to facilitate ER-to-Golgi transport and proteolytic activation of SREBPs. When ER cholesterol is above a threshold concentration, this transport is blo

SUBMITTER: Williams BC 

PROVIDER: S-EPMC12773782 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature