3W67

Crystal structure of mouse alpha-tocopherol transfer protein in complex with alpha-tocopherol and phosphatidylinositol-(3,4)-bisphosphate

Summary for 3W67

• Entry DOI: 10.2210/pdb3w67/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)-hydroxy{[(1S,2R,3R,4S,5S,6S)-2,3,6-trihydroxy-4,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dibutanoate, ... (4 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: 126757.40

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 (2.61 Å)