3W68

Crystal structure of mouse alpha-tocopherol transfer protein in complex with alpha-tocopherol and phosphatidylinositol-(4,5)-bisphosphate

Summary for 3W68

• Entry DOI: 10.2210/pdb3w68/pdb
• Related: 3w67
• Descriptor: Alpha-tocopherol transfer protein, (2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL, (2R)-3-{[(S)-{[(2S,3R,5S,6S)-2,6-DIHYDROXY-3,4,5-TRIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-2-(1-HYDROXY BUTOXY)PROPYL BUTYRATE, ... (6 entities in total)
• Functional Keywords: ataxia, vitamin e deficiency, aved, transfer protein, tocopherol, vitamin e, disease mutation, alpha-tocopherol transfer, alpha-tocopherol, phosphatidyl inositol phosphates, transport protein
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm (By similarity): Q8BWP5
• Total number of polymer chains: 4
• Total formula weight: 127383.27

Authors

Ohto, U.,Satow, Y. (deposition date: 2013-02-11, release date: 2013-05-01, Last modification date: 2023-11-08)

Primary citation

Kono, N.,Ohto, U.,Hiramatsu, T.,Urabe, M.,Uchida, Y.,Satow, Y.,Arai, H.
Impaired alpha-TTP-PIPs interaction underlies familial vitamin E deficiency
Science, 340:1106-1110, 2013

PubMed Abstract: α-Tocopherol (vitamin E) transfer protein (α-TTP) regulates the secretion of α-tocopherol from liver cells. Missense mutations of some arginine residues at the surface of α-TTP cause severe vitamin E deficiency in humans, but the role of these residues is unclear. Here, we found that wild-type α-TTP bound phosphatidylinositol phosphates (PIPs), whereas the arginine mutants did not. In addition, PIPs in the target membrane promoted the intermembrane transfer of α-tocopherol by α-TTP. The crystal structure of the α-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 α-tocopherol-binding pocket to open. Thus, PIPs have a role in promoting the release of a ligand from a lipid-transfer protein.

PubMed: 23599266
DOI: 10.1126/science.1233508

Experimental method

X-RAY DIFFRACTION (2.05 Å)