5MUG
Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
Summary for 5MUG
| Entry DOI | 10.2210/pdb5mug/pdb |
| Descriptor | 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) |
| Functional Keywords | lipid transfer protein, sec14-like, transport protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 27556.74 |
| Authors | Stocker, A.,Aeschimann, W. (deposition date: 2017-01-13, release date: 2017-07-19, Last modification date: 2024-10-09) |
| Primary citation | 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 Cited by 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: 28694484DOI: 10.1038/s41598-017-05148-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.42 Å) |
Structure validation
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