1OIP

The Molecular Basis of Vitamin E Retention: Structure of Human Alpha-Tocopherol Transfer Protein

Summary for 1OIP

• Entry DOI: 10.2210/pdb1oip/pdb
• Related: 1OIZ 1R5L
• Descriptor: ALPHA-TOCOPHEROL TRANSFER PROTEIN, SULFATE ION, (2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL, ... (4 entities in total)
• Functional Keywords: transport, ataxia, aved, transfer protein, tocopherol, vitamin e transport, disease mutation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P49638
• Total number of polymer chains: 1
• Total formula weight: 32414.48

Authors

Meier, R.,Tomizaki, T.,Schulze-Briese, C.,Baumann, U.,Stocker, A. (deposition date: 2003-06-24, release date: 2004-01-14, Last modification date: 2024-05-08)

Primary citation

Meier, R.,Tomizaki, T.,Schulze-Briese, C.,Baumann, U.,Stocker, A.
The Molecular Basis of Vitamin E Retention: Structure of Human Alpha-Tocopherol Transfer Protein
J.Mol.Biol., 331:725-, 2003

PubMed Abstract: Alpha-tocopherol transfer protein (alpha-TTP) is a liver protein responsible for the selective retention of alpha-tocopherol from dietary vitamin E, which is a mixture of alpha, beta, gamma, and delta-tocopherols and the corresponding tocotrienols. The alpha-TTP-mediated transfer of alpha-tocopherol into nascent VLDL is the major determinant of plasma alpha-tocopherol levels in humans. Mutations in the alpha-TTP gene have been detected in patients suffering from low plasma alpha-tocopherol and ataxia with isolated vitamin E deficiency (AVED). The crystal structure of alpha-TTP reveals two conformations. In its closed tocopherol-charged form, a mobile helical surface segment seals the hydrophobic binding pocket. In the presence of detergents, an open conformation is observed, which probably represents the membrane-bound form. The selectivity of alpha-TTP for RRR-alpha-tocopherol is explained from the van der Waals contacts occurring in the lipid-binding pocket. Mapping the known mutations leading to AVED onto the crystal structure shows that no mutations occur directly in the binding pocket.

PubMed: 12899840
DOI: 10.1016/S0022-2836(03)00724-1

Experimental method

X-RAY DIFFRACTION (1.95 Å)