| Literature DB >> 30581148 |
Huan Wang1, Qianli Ma2, Yanfei Qi2, Jiangqing Dong1, Ximing Du2, James Rae3, Jue Wang4, Wei-Feng Wu4, Andrew J Brown2, Robert G Parton3, Jia-Wei Wu5, Hongyuan Yang6.
Abstract
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.Entities:
Keywords: OCRL; ORP1; ORP5; OSBP; PI(4,5)P(2); PI4P; cholesterol; membrane contact sites; oxysterol binding protein; phosphoinositides
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Year: 2018 PMID： 30581148 DOI： 10.1016/j.molcel.2018.11.014
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970