The crystal structure of ORP3 reveals the conservative PI4P binding pattern
- PMID: 32819557
- DOI: 10.1016/j.bbrc.2020.06.090
The crystal structure of ORP3 reveals the conservative PI4P binding pattern
Abstract
Oxysterol-binding protein (OSBP) and its related protein (ORP) constitute a conserved family of lipid transfer proteins (LTPs). ORPs have been implicated as intracellular lipid exchanger and sensor in recent years, which regulate the lipid homeostasis and signal pathway. OSBP-related protein 3 plays key role in controlling cell adhesion and migration and could be developed as the drug target for cancer therapy. Here, we report the crystal structures of human ORP3 ORD to 2.1 Å and ORD-PI4P complex to 3.2 Å. The binding assay in vitro confirms the ORP3 has the capability of PI4P binding. This study further verifies that the PI4P is the common ligand of all ORPs and ORPs should be the lipid exchanger in membrane contact sites(MCS).
Keywords: ORP3; OSBP-Related domain; Oxysterol-binding protein; PI4P.
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.
Similar articles
-
Structure of human ORP3 ORD reveals conservation of a key function and ligand specificity in OSBP-related proteins.PLoS One. 2021 Apr 15;16(4):e0248781. doi: 10.1371/journal.pone.0248781. eCollection 2021. PLoS One. 2021. PMID: 33857182 Free PMC article.
-
Oxysterol-binding protein-related protein (ORP) 6 localizes to the ER and ER-plasma membrane contact sites and is involved in the turnover of PI4P in cerebellar granule neurons.Exp Cell Res. 2018 Sep 15;370(2):601-612. doi: 10.1016/j.yexcr.2018.07.025. Epub 2018 Jul 18. Exp Cell Res. 2018. PMID: 30028970
-
Oxysterol-binding proteins: sterol and phosphoinositide sensors coordinating transport, signaling and metabolism.Prog Lipid Res. 2013 Oct;52(4):529-38. doi: 10.1016/j.plipres.2013.06.004. Epub 2013 Jul 2. Prog Lipid Res. 2013. PMID: 23830809 Review.
-
A vertebrate model for the study of lipid binding/transfer protein function: conservation of OSBP-related proteins between zebrafish and human.Biochem Biophys Res Commun. 2014 Apr 11;446(3):675-80. doi: 10.1016/j.bbrc.2013.12.002. Epub 2013 Dec 8. Biochem Biophys Res Commun. 2014. PMID: 24326072
-
OSBP-Related Protein Family: Mediators of Lipid Transport and Signaling at Membrane Contact Sites.Int Rev Cell Mol Biol. 2016;321:299-340. doi: 10.1016/bs.ircmb.2015.09.006. Epub 2015 Nov 18. Int Rev Cell Mol Biol. 2016. PMID: 26811291 Review.
Cited by
-
Crystal Structure of the ORP8 Lipid Transport ORD Domain: Model of Lipid Transport.Cells. 2023 Jul 31;12(15):1974. doi: 10.3390/cells12151974. Cells. 2023. PMID: 37566053 Free PMC article.
-
Extracellular membrane particles en route to the nucleus - exploring the VOR complex.Biochem Soc Trans. 2025 Jun 30;53(3):529-546. doi: 10.1042/BST20253005. Biochem Soc Trans. 2025. PMID: 40366329 Free PMC article. Review.
-
Structure of human ORP3 ORD reveals conservation of a key function and ligand specificity in OSBP-related proteins.PLoS One. 2021 Apr 15;16(4):e0248781. doi: 10.1371/journal.pone.0248781. eCollection 2021. PLoS One. 2021. PMID: 33857182 Free PMC article.
-
Uncovering the Mechanisms of Intracellular Membrane Trafficking by Reconstituted Membrane Systems.Membranes (Basel). 2025 May 16;15(5):154. doi: 10.3390/membranes15050154. Membranes (Basel). 2025. PMID: 40422764 Free PMC article. Review.
-
Endoplasmic Reticulum-Plasma Membrane Contact Sites: Regulators, Mechanisms, and Physiological Functions.Front Cell Dev Biol. 2021 Feb 4;9:627700. doi: 10.3389/fcell.2021.627700. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 33614657 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
