Supernatant protein factor in complex with RRR-alpha-tocopherylquinone: a link between oxidized Vitamin E and cholesterol biosynthesis.

Stocker, Achim; Baumann, Ulrich (2003). Supernatant protein factor in complex with RRR-alpha-tocopherylquinone: a link between oxidized Vitamin E and cholesterol biosynthesis. Journal of molecular biology, 332(4), pp. 759-765. Elsevier 10.1016/s0022-2836(03)00924-0

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Stocker, Achim and Baumann, Ulrich

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0022-2836

Publisher:

Elsevier

Language:

English

Submitter:

Anja Ebeling

Date Deposited:

11 Mar 2020 16:27

Last Modified:

11 Mar 2020 16:27

Publisher DOI:

10.1016/s0022-2836(03)00924-0

PubMed ID:

12972248

BORIS DOI:

10.7892/boris.141812

URI:

https://boris.unibe.ch/id/eprint/141812

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