5U77

Crystal structure of ORP8 PH domain

5U77 の概要

• エントリーDOI: 10.2210/pdb5u77/pdb
• 関連するPDBエントリー: 5U78
• 分子名称: Oxysterol-binding protein-related protein 8, N-(2-hydroxyethyl)-N,N-dimethyl-3-sulfopropan-1-aminium, FORMIC ACID, ... (4 entities in total)
• 機能のキーワード: oxsyterol, lipid transport, membrane contact site, phosphoinositide
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13868.29

構造登録者

Ghai, R.,Yang, H. (登録日: 2016-12-11, 公開日: 2017-10-18, 最終更新日: 2023-10-04)

主引用文献

Ghai, R.,Du, X.,Wang, H.,Dong, J.,Ferguson, C.,Brown, A.J.,Parton, R.G.,Wu, J.W.,Yang, H.
ORP5 and ORP8 bind phosphatidylinositol-4, 5-biphosphate (PtdIns(4,5)P 2) and regulate its level at the plasma membrane.
Nat Commun, 8:757-757, 2017

PubMed Abstract: ORP5 and ORP8, members of the oxysterol-binding protein (OSBP)-related proteins (ORP) family, are endoplasmic reticulum membrane proteins implicated in lipid trafficking. ORP5 and ORP8 are reported to localize to endoplasmic reticulum-plasma membrane junctions via binding to phosphatidylinositol-4-phosphate (PtdIns(4)P), and act as a PtdIns(4)P/phosphatidylserine counter exchanger between the endoplasmic reticulum and plasma membrane. Here we provide evidence that the pleckstrin homology domain of ORP5/8 via PtdIns(4,5)P , and not PtdIns(4)P binding mediates the recruitment of ORP5/8 to endoplasmic reticulum-plasma membrane contact sites. The OSBP-related domain of ORP8 can extract and transport multiple phosphoinositides in vitro, and knocking down both ORP5 and ORP8 in cells increases the plasma membrane level of PtdIns(4,5)P with little effect on PtdIns(4)P. Overall, our data show, for the first time, that phosphoinositides other than PtdIns(4)P can also serve as co-exchangers for the transport of cargo lipids by ORPs.ORP5/8 are endoplasmic reticulum (ER) membrane proteins implicated in lipid trafficking that localize to ER-plasma membrane (PM) contacts and maintain membrane homeostasis. Here the authors show that PtdIns(4,5)P plays a critical role in the targeting and function of ORP5/8 at the PM.

PubMed: 28970484
DOI: 10.1038/s41467-017-00861-5

実験手法

X-RAY DIFFRACTION (2.157 Å)