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

Meier, Reto; Tomizaki, Takashi; Schulze-Briese, Clemens; Baumann, Ulrich; Stocker, Achim (2003). The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein. Journal of molecular biology, 331(3), pp. 725-734. Elsevier 10.1016/s0022-2836(03)00724-1

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Stocker, Achim

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 16:19

Last Modified:

11 Mar 2020 16:21

Publisher DOI:

10.1016/s0022-2836(03)00724-1

PubMed ID:

12899840

BORIS DOI:

10.7892/boris.141800

URI:

https://boris.unibe.ch/id/eprint/141800

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