Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency

Nozomu Kono, Umeharu Ohto, Tatsufumi Hiramatsu, Michiko Urabe, Yasunori Uchida, Yoshinori Satow, Hiroyuki Arai

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

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.

Original languageEnglish
Pages (from-to)1106-1110
Number of pages5
JournalScience
Volume340
Issue number6136
DOIs
StatePublished - 31 May 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency'. Together they form a unique fingerprint.

Cite this