磷脂酰肌醇
胆固醇
圆周率
生物
氧甾醇
调节器
植物脂质转运蛋白
磷脂酰肌醇4,5-二磷酸
细胞生物学
生物化学
信号转导
基因
作者
Huan Wang,Qianli Ma,Yanfei Qi,Jiangqing Dong,Ximing Du,James M. Rae,Jue Wang,Weifeng Wu,Andrew J. Brown,Robert G. Parton,Jia-Wei Wu,Hongyuan Yang
出处
期刊:Molecular Cell
[Elsevier]
日期:2019-02-01
卷期号:73 (3): 458-473.e7
被引量:95
标识
DOI:10.1016/j.molcel.2018.11.014
摘要
Cholesterol is highly enriched at the plasma membrane (PM), and lipid transfer proteins may deliver cholesterol to the PM in a nonvesicular manner. Here, through a mini-screen, we identified the oxysterol binding protein (OSBP)-related protein 2 (ORP2) as a novel mediator of selective cholesterol delivery to the PM. Interestingly, ORP2-mediated enrichment of PM cholesterol was coupled with the removal of phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2) from the PM. ORP2 overexpression or deficiency impacted the levels of PM cholesterol and PI(4,5)P2, and ORP2 efficiently transferred both cholesterol and PI(4,5)P2in vitro. We determined the structure of ORP2 in complex with PI(4,5)P2 at 2.7 Å resolution. ORP2 formed a stable tetramer in the presence of PI(4,5)P2, and tetramerization was required for ORP2 to transfer PI(4,5)P2. Our results identify a novel pathway for cholesterol delivery to the PM and establish ORP2 as a key regulator of both cholesterol and PI(4,5)P2 of the PM.
科研通智能强力驱动
Strongly Powered by AbleSci AI