Molecule of the Month
April 2021
Engineering of a Functional γ-Tocopherol Transfer Protein
  1. Atomic model of the engineered γ-TTP nano-spherical particle
  2. Zoom of the γ-tocopherol binding pocket with all residues visualized

α-Tocopherol Transfer Protein (α-TTP) sequesters α-tocopherol out of eight naturally occurring Vitamin E isomers in man [1]. The reasons for the preferential α-tocopherol homeostasis over the similarly abundant γ-tocopherol isomer are currently not known.
In this work, we describe the engineering of a biophysically functional TTP variant with its vitamer selectivity shifted towards γ-tocopherol [2]. Using primary human umbilical vein cells (HUVEC) it is shown that α-TTP significantly reduces cytokine-induced mRNA expression of the pro-inflammatory cytokines IL6, CCL2, TNF and ICAM1 while γ-TTP is not able to attenuate cytokine-mediated transcription. The observed differences indicate that cytokine suppression occurs primarily in the presence of α-tocopherol and also provide clues on the preferential homeostasis of the later in man.

This work was carried out in the group of Prof. Achim Stocker.


  1. K. Ouahchi, M. Arita, H. Kayden, F. Hentati, M. B. Hamida, R. Sokol, H. Arai, K. Inoue, J.-L. Mandel, M. Koenig;
    "Ataxia with isolated vitamin E deficiency is caused by mutations in the α-tocopherol transfer protein"
    Nature Genetics, 1995, 9(2), 141-145; doi:10.1038/ng0295-141.
  2. W. Aeschimann, S. Kammer, S. Staats, P. Schneider, G. Schneider, G. Rimbach, M. Cascella, A. Stocker;
    "Engineering of a functional γ-tocopherol transfer protein"
    Redox Biology, 2021, 38, 101773/1-12; doi:10.1016/j.redox.2020.101773.