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The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein.
Journal article

The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein.

  • 2003-08-06
Published in:
  • Journal of molecular biology. - 2003
Ataxia
Binding Sites
Biological Transport
Carrier Proteins
Crystallography, X-Ray
Humans
Ligands
Lipid Metabolism
Models, Molecular
Protein Conformation
Retinitis Pigmentosa
Substrate Specificity
Vitamin E
Vitamin E Deficiency
alpha-Tocopherol
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/131291
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