1OLM

Supernatant Protein Factor in Complex with RRR-alpha-Tocopherylquinone: A Link between Oxidized Vitamin E and Cholesterol Biosynthesis

Summary for 1OLM

• Entry DOI: 10.2210/pdb1olm/pdb
• Related: 1O6U
• Descriptor: SEC14-LIKE PROTEIN 2, RRR-ALPHA-TOCOPHERYLQUINONE, ... (4 entities in total)
• Functional Keywords: lipid-binding protein, cholesterol biosynthesis, oxidized vitamin e, lipid-binding, transport, transcription regulation, activator, lipid binding protein
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: O76054 O76054
• Total number of polymer chains: 3
• Total formula weight: 139992.65

Authors

Stocker, A.,Baumann, U. (deposition date: 2003-08-08, release date: 2004-08-12, Last modification date: 2024-05-08)

Primary citation

Stocker, A.,Baumann, U.
Supernatant Protein Factor in Complex with Rrr-Alpha-Tocopherylquinone: A Link between Oxidized Vitamin E and Cholesterol Biosynthesis
J.Mol.Biol., 332:759-, 2003

PubMed Abstract: The vast majority of monomeric lipid transport in nature is performed by lipid-specific protein carriers. This class of proteins can enclose cognate lipid molecules in a hydrophobic cavity and transport them across the aqueous environment. Supernatant protein factor (SPF) is an enigmatic representative of monomeric lipid transporters belonging to the SEC14 family. SPF stimulates squalene epoxidation, a downstream step of the cholesterol biosynthetic pathway, by an unknown mechanism. Here, we present the three-dimensional crystal structure of human SPF in complex with RRR-alpha-tocopherylquinone, the major physiological oxidation product of RRR-alpha-tocopherol, at a resolution of 1.95A. The structure of the complex reveals how SPF sequesters RRR-alpha-tocopherylquinone (RRR-alpha-TQ) in its protein body and permits a comparison with the recently solved structure of human alpha-tocopherol transfer protein (alpha-TTP) in complex with RRR-alpha-tocopherol. Recent findings have shown that RRR-alpha-TQ is reduced in vivo to RRR-alpha-TQH(2), the latter has been suggested to protect low-density lipoprotein (LDL) particles from oxidation. Hence, the antioxidant function of the redox couple RRR-alpha-TQ/RRR-alpha-TQH(2) in blocking LDL oxidation may reduce cellular cholesterol uptake and thus explain how SPF upregulates cholesterol synthesis.

PubMed: 12972248
DOI: 10.1016/S0022-2836(03)00924-0

Experimental method

X-RAY DIFFRACTION (1.95 Å)