Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier.
- Aeschimann W University of Bern, Department of Chemistry and Biochemistry, Bern, Switzerland.
- Staats S University of Kiel, Institute of Human Nutrition and Food Science, Kiel, Germany.
- Kammer S University of Bern, Department of Chemistry and Biochemistry, Bern, Switzerland.
- Olieric N Paul Scherrer Institut, Villigen, Switzerland.
- Jeckelmann JM University of Bern, Institute of Biochemistry and Molecular Medicine, Bern, Switzerland.
- Fotiadis D University of Bern, Institute of Biochemistry and Molecular Medicine, Bern, Switzerland.
- Netscher T DSM Nutritional Products Ltd., Basel, Switzerland.
- Rimbach G University of Kiel, Institute of Human Nutrition and Food Science, Kiel, Germany.
- Cascella M University of Oslo, Department of Chemistry and Centre for Theoretical and Computational Chemistry (CTCC), Oslo, Norway. michele.cascella@kjemi.uio.no.
- Stocker A University of Bern, Department of Chemistry and Biochemistry, Bern, Switzerland. achim.stocker@dcb.unibe.ch.
- 2017-07-12
Published in:
- Scientific reports. - 2017
Caco-2 Cells
Carrier Proteins
Crystallography, X-Ray
Endosomes
Endothelial Cells
Epithelial Cells
Human Umbilical Vein Endothelial Cells
Humans
Models, Molecular
Nanoparticles
Protein Aggregates
Protein Conformation
Protein Folding
Protein Multimerization
Protein Stability
Thermodynamics
alpha-Tocopherol
English
Vitamin E is one of the most important natural antioxidants, protecting polyunsaturated fatty acids in the membranes of cells. Among different chemical isoforms assimilated from dietary regimes, RRR-α-tocopherol is the only one retained in higher animals. This is possible thanks to α-Tocopherol Transfer Protein (α-TTP), which extracts α-tocopherol from endosomal compartments in liver cells, facilitating its distribution into the body. Here we show that, upon binding to its substrate, α-TTP acquires tendency to aggregation into thermodynamically stable high molecular weight oligomers. Determination of the structure of such aggregates by X-ray crystallography revealed a spheroidal particle formed by 24 protein monomers. Oligomerization is triggered by refolding of the N-terminus. Experiments with cultured cell monolayers demonstrate that the same oligomers are efficiently transported through an endothelial barrier (HUVEC) and not through an epithelial one (Caco-2). Discovery of a human endogenous transport protein with intrinsic capability of crossing endothelial tissues opens to new ways of drug delivery into the brain or other tissues protected by endothelial barriers.
- Language
-
- English
- Open access status
- gold
- Identifiers
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- DOI 10.1038/s41598-017-05148-9
- PMID 28694484
- Persistent URL
- https://sonar.ch/global/documents/184926
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