5ZM8

Crystal structure of ORP2-ORD in complex with PI(4,5)P2

Summary for 5ZM8

• Entry DOI: 10.2210/pdb5zm8/pdb
• Descriptor: Oxysterol-binding protein-related protein 2, [(2~{S})-1-octadecanoyloxy-3-[oxidanyl-[(1~{R},2~{R},3~{S},4~{S},5~{S},6~{S})-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propan-2-yl] icosa-5,8,11,14-tetraenoate (3 entities in total)
• Functional Keywords: transporter, complex, phospholipid, lipid transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 107641.47

Authors

Wang, H.,Dong, J.Q.,Wang, J.,Wu, J.W. (deposition date: 2018-04-01, release date: 2019-01-02, Last modification date: 2023-11-22)

Primary citation

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.
ORP2 Delivers Cholesterol to the Plasma Membrane in Exchange for Phosphatidylinositol 4, 5-Bisphosphate (PI(4,5)P2).
Mol. Cell, 73:458-473.e7, 2019

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) from the PM. ORP2 overexpression or deficiency impacted the levels of PM cholesterol and PI(4,5)P, and ORP2 efficiently transferred both cholesterol and PI(4,5)Pin vitro. We determined the structure of ORP2 in complex with PI(4,5)P at 2.7 Å resolution. ORP2 formed a stable tetramer in the presence of PI(4,5)P, and tetramerization was required for ORP2 to transfer PI(4,5)P. 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 of the PM.

PubMed: 30581148
DOI: 10.1016/j.molcel.2018.11.014

Experimental method

X-RAY DIFFRACTION (2.7 Å)