5zm8
From Proteopedia
Crystal structure of ORP2-ORD in complex with PI(4,5)P2
Structural highlights
DiseaseOSBL2_HUMAN Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry. FunctionOSBL2_HUMAN Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate (PubMed:11279184). Binds 25-hydroxycholesterol (PubMed:17428193).[1] [2] Publication Abstract from PubMedCholesterol 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 A 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. ORP2 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 WF, Brown AJ, Parton RG, Wu JW, Yang H Mol Cell. 2018 Dec 10. pii: S1097-2765(18)30984-5. doi:, 10.1016/j.molcel.2018.11.014. PMID:30581148[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
Categories: Homo sapiens | Large Structures | Dong JQ | Wang H | Wang J | Wu JW