1OLM: Supernatant Protein Factor In Complex With Rrr-Alpha-Tocopherylquinone: A Link Between Oxidized Vitamin E And Cholesterol Biosynthesis

Citation:
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.
PDB ID: 1OLMDownload
MMDB ID: 28860
PDB Deposition Date: 2003/8/8
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 1OLM: monomeric; determined by author and by software (PQS)
Molecular Components in 1OLM
Label Count Molecule
Protein (1 molecule)
1
Sec14-like Protein 2(Gene symbol: SEC14L2)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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