1olm

SUPERNATANT PROTEIN FACTOR IN COMPLEX WITH RRR-ALPHA-TOCOPHERYLQUINONE: A LINK BETWEEN OXIDIZED VITAMIN E AND CHOLESTEROL BIOSYNTHESIS

Overview

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.

About this Structure

1OLM is a Protein complex structure of sequences from Homo sapiens with VTQ as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Supernatant protein factor in complex with RRR-alpha-tocopherylquinone: a link between oxidized Vitamin E and cholesterol biosynthesis., Stocker A, Baumann U, J Mol Biol. 2003 Sep 26;332(4):759-65. PMID:12972248

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