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From Proteopedia
The Molecular Basis of Vitamin E Retention: Structure of Human Alpha-Tocopherol Transfer Protein
Structural highlights
Disease[TTPA_HUMAN] Defects in TTPA are the cause of ataxia with isolated vitamin E deficiency (AVED) [MIM:277460]. AVED is an autosomal recessive disease characterized by spinocerebellar degeneration. It causes ataxia and peripheral neuropathy that resembles Friedreich ataxia. AVED patients have markedly reduced plasma levels of vitamin E.[1] [2] [3] [4] [5] [6] Function[TTPA_HUMAN] Binds alpha-tocopherol and enhances its transfer between separate membranes. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAlpha-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. The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein.,Meier R, Tomizaki T, Schulze-Briese C, Baumann U, Stocker A J Mol Biol. 2003 Aug 15;331(3):725-34. PMID:12899840[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Baumann, U | Meier, R | Schulze-Briese, C | Stocker, A | Tomizaki, T | Ataxia | Aved | Tocopherol | Transfer protein | Transport | Vitamin e
