| First Author | Kono N | Year | 2013 |
| Journal | Science | Volume | 340 |
| Issue | 6136 | Pages | 1106-10 |
| PubMed ID | 23599266 | Mgi Jnum | J:197682 |
| Mgi Id | MGI:5494336 | Doi | 10.1126/science.1233508 |
| Citation | Kono N, et al. (2013) Impaired alpha-TTP-PIPs interaction underlies familial vitamin E deficiency. Science 340(6136):1106-10 |
| abstractText | alpha-Tocopherol (vitamin E) transfer protein (alpha-TTP) regulates the secretion of alpha-tocopherol from liver cells. Missense mutations of some arginine residues at the surface of alpha-TTP cause severe vitamin E deficiency in humans, but the role of these residues is unclear. Here, we found that wild-type alpha-TTP bound phosphatidylinositol phosphates (PIPs), whereas the arginine mutants did not. In addition, PIPs in the target membrane promoted the intermembrane transfer of alpha-tocopherol by alpha-TTP. The crystal structure of the alpha-TTP-PIPs complex revealed that the disease-related arginine residues interacted with phosphate groups of the PIPs and that the PIPs binding caused the lid of the alpha-tocopherol-binding pocket to open. Thus, PIPs have a role in promoting the release of a ligand from a lipid-transfer protein. |
