5ZM7

Crystal structure of ORP1-ORD in complex with cholesterol at 3.4 A resolution

5ZM7 の概要

• エントリーDOI: 10.2210/pdb5zm7/pdb
• 分子名称: Oxysterol-binding protein-related protein 1, CHOLESTEROL (2 entities in total)
• 機能のキーワード: transporter, complex, lipid, lipid transport
• 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: 50914.97

構造登録者

Dong, J.,Wang, J.,Wu, J.W. (登録日: 2018-04-01, 公開日: 2019-02-27, 最終更新日: 2023-11-22)

主引用文献

Dong, J.,Du, X.,Wang, H.,Wang, J.,Lu, C.,Chen, X.,Zhu, Z.,Luo, Z.,Yu, L.,Brown, A.J.,Yang, H.,Wu, J.W.
Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2.
Nat Commun, 10:829-829, 2019

PubMed Abstract: Phosphatidylinositol phosphates (PIPs) and cholesterol are known to regulate the function of late endosomes and lysosomes (LELs), and ORP1L specifically localizes to LELs. Here, we show in vitro that ORP1 is a PI(4,5)P- or PI(3,4)P-dependent cholesterol transporter, but cannot transport any PIPs. In cells, both ORP1L and PI(3,4)P are required for the efficient removal of cholesterol from LELs. Structures of the lipid-binding domain of ORP1 (ORP1-ORD) in complex with cholesterol or PI(4,5)P display open conformations essential for ORP function. PI(4,5)P/PI(3,4)P can facilitate ORP1-mediated cholesterol transport by promoting membrane targeting and cholesterol extraction. Thus, our work unveils a distinct mechanism by which PIPs may allosterically enhance OSBP/ORPs-mediated transport of major lipid species such as cholesterol.

PubMed: 30783101
DOI: 10.1038/s41467-019-08791-0

実験手法

X-RAY DIFFRACTION (3.401 Å)