Download MendeleyORP2 Delivers Cholesterol to the Plasma Membrane in Exchange for Phosphatidylinositol 4, 5-Bisphosphate (PI(4,5)P2).
Wang, H., Ma, Q., Qi, Y., Dong, J., Du, X., Rae, J., Wang, J., Wu, W.F., Brown, A.J., Parton, R.G., Wu, J.W., Yang, H.(2019) Mol Cell 73: 458-473.e7
- PubMed: 30581148
- DOI: https://doi.org/10.1016/j.molcel.2018.11.014
- Primary Citation of Related Structures:
5ZM8 - PubMed 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)P 2 ) from the PM. ORP2 overexpression or deficiency impacted the levels of PM cholesterol and PI(4,5)P 2 , and ORP2 efficiently transferred both cholesterol and PI(4,5)P 2 in?vitro. We determined the structure of ORP2 in complex with PI(4,5)P 2 at 2.7?? resolution. ORP2 formed a stable tetramer in the presence of PI(4,5)P 2 , and tetramerization was required for ORP2 to transfer PI(4,5)P 2 . 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)P 2 of the PM.
Organizational Affiliation:
Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory for Protein Science, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
