3SPW

Structure of Osh4p/Kes1p in complex with phosphatidylinositol 4-phosphate

3SPW の概要

• エントリーDOI: 10.2210/pdb3spw/pdb
• 関連するPDBエントリー: 1ZHZ
• 分子名称: Protein KES1, (2R)-1-(heptadecanoyloxy)-3-{[(R)-hydroxy{[(1R,2R,3R,4R,5S,6R)-2,3,5,6-tetrahydroxy-4-(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate (3 entities in total)
• 機能のキーワード: lipid binding protein, protein binding
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 101310.21

構造登録者

Delfosse, V.,de Saint-Jean, M.,Douguet, D.,Antonny, B.,Drin, G.,Bourguet, W. (登録日: 2011-07-04, 公開日: 2011-11-23, 最終更新日: 2023-09-13)

主引用文献

de Saint-Jean, M.,Delfosse, V.,Douguet, D.,Chicanne, G.,Payrastre, B.,Bourguet, W.,Antonny, B.,Drin, G.
Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers.
J.Cell Biol., 195:965-978, 2011

PubMed Abstract: Osh/Orp proteins transport sterols between organelles and are involved in phosphoinositide metabolism. The link between these two aspects remains elusive. Using novel assays, we address the influence of membrane composition on the ability of Osh4p/Kes1p to extract, deliver, or transport dehydroergosterol (DHE). Surprisingly, phosphatidylinositol 4-phosphate (PI(4)P) specifically inhibited DHE extraction because PI(4)P was itself efficiently extracted by Osh4p. We solve the structure of the Osh4p-PI(4)P complex and reveal how Osh4p selectively substitutes PI(4)P for sterol. Last, we show that Osh4p quickly exchanges DHE for PI(4)P and, thereby, can transport these two lipids between membranes along opposite routes. These results suggest a model in which Osh4p transports sterol from the ER to late compartments pinpointed by PI(4)P and, in turn, transports PI(4)P backward. Coupled to PI(4)P metabolism, this transport cycle would create sterol gradients. Because the residues that recognize PI(4)P are conserved in Osh4p homologues, other Osh/Orp are potential sterol/phosphoinositol phosphate exchangers.

PubMed: 22162133
DOI: 10.1083/jcb.201104062

実験手法

X-RAY DIFFRACTION (2.6 Å)