5mug
From Proteopedia
Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
Structural highlights
Disease[TTPA_HUMAN] Defects in TTPA are the cause of ataxia with isolated vitamin E deficiency (AVED) [MIM:277460]. AVED is an autosomal recessive disease characterized by spinocerebellar degeneration. It causes ataxia and peripheral neuropathy that resembles Friedreich ataxia. AVED patients have markedly reduced plasma levels of vitamin E.[1] [2] [3] [4] [5] [6] Function[TTPA_HUMAN] Binds alpha-tocopherol and enhances its transfer between separate membranes. Publication Abstract from PubMedVitamin 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-alpha-tocopherol is the only one retained in higher animals. This is possible thanks to alpha-Tocopherol Transfer Protein (alpha-TTP), which extracts alpha-tocopherol from endosomal compartments in liver cells, facilitating its distribution into the body. Here we show that, upon binding to its substrate, alpha-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. Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier.,Aeschimann W, Staats S, Kammer S, Olieric N, Jeckelmann JM, Fotiadis D, Netscher T, Rimbach G, Cascella M, Stocker A Sci Rep. 2017 Jul 10;7(1):4970. doi: 10.1038/s41598-017-05148-9. PMID:28694484[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
