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Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain.
- Source :
-
Molecular cell [Mol Cell] 2004 Jul 23; Vol. 15 (2), pp. 259-68. - Publication Year :
- 2004
-
Abstract
- Mammalian cells control their membrane composition by regulating the vesicular transport of membrane-bound sterol regulatory element binding proteins (SREBPs) from endoplasmic reticulum (ER) to Golgi. Transport is blocked by cholesterol, which triggers SCAP, the SREBP escort protein, to bind to Insigs, which are ER retention proteins. The cholesterol trigger mechanism is unknown. Using recombinant SCAP purified in detergent, we show that cholesterol acts by binding with high affinity and specificity to the 767 amino acid octahelical membrane region of SCAP. This octahelical region contains a conserved pentahelical sterol-sensing domain found in six other polytopic membrane proteins. We show that the membrane domain of SCAP is a tetramer and that cholesterol binding is inhibited by cationic amphiphiles, raising the possibility of allosteric regulation by positively charged phospholipids. The current studies show that cells control their cholesterol content through receptor-ligand interactions and not through changes in the physical properties of the membrane.
- Subjects :
- Allosteric Regulation
Animals
Binding Sites
Cricetinae
Detergents metabolism
Drosophila melanogaster metabolism
Intracellular Signaling Peptides and Proteins
Phospholipids metabolism
Protein Binding
Protein Structure, Tertiary
Recombinant Proteins genetics
Recombinant Proteins isolation & purification
Recombinant Proteins metabolism
Rhodopsin metabolism
Sensitivity and Specificity
Sterols metabolism
Cell Membrane metabolism
Cholesterol metabolism
Membrane Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-2765
- Volume :
- 15
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 15260976
- Full Text :
- https://doi.org/10.1016/j.molcel.2004.06.019