5MUG

Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier

5MUG の概要

• エントリーDOI: 10.2210/pdb5mug/pdb
• 分子名称: Alpha-tocopherol transfer protein, (2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: lipid transfer protein, sec14-like, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27556.74

構造登録者

Stocker, A.,Aeschimann, W. (登録日: 2017-01-13, 公開日: 2017-07-19, 最終更新日: 2024-10-09)

主引用文献

Aeschimann, W.,Staats, S.,Kammer, S.,Olieric, N.,Jeckelmann, J.M.,Fotiadis, D.,Netscher, T.,Rimbach, G.,Cascella, M.,Stocker, A.
Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier.
Sci Rep, 7:4970-4970, 2017

PubMed Abstract: 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.

PubMed: 28694484
DOI: 10.1038/s41598-017-05148-9

実験手法

X-RAY DIFFRACTION (2.42 Å)