| Structural highlights
Disease
OSBL2_HUMAN Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry.
Function
OSBL2_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 PubMed
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 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
- ↑ Xu Y, Liu Y, Ridgway ND, McMaster CR. Novel members of the human oxysterol-binding protein family bind phospholipids and regulate vesicle transport. J Biol Chem. 2001 May 25;276(21):18407-14. Epub 2001 Feb 26. PMID:11279184 doi:http://dx.doi.org/10.1074/jbc.M101204200
- ↑ Suchanek M, Hynynen R, Wohlfahrt G, Lehto M, Johansson M, Saarinen H, Radzikowska A, Thiele C, Olkkonen VM. The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket. Biochem J. 2007 Aug 1;405(3):473-80. PMID:17428193 doi:http://dx.doi.org/10.1042/BJ20070176
- ↑ Wang H, Ma Q, Qi Y, Dong J, Du X, Rae J, Wang J, Wu WF, Brown AJ, Parton RG, Wu JW, Yang H. ORP2 Delivers Cholesterol to the Plasma Membrane in Exchange for Phosphatidylinositol 4, 5-Bisphosphate (PI(4,5)P2). Mol Cell. 2018 Dec 10. pii: S1097-2765(18)30984-5. doi:, 10.1016/j.molcel.2018.11.014. PMID:30581148 doi:http://dx.doi.org/10.1016/j.molcel.2018.11.014
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