4PH7

Structure of Osh6p in complex with phosphatidylinositol 4-phosphate

Summary for 4PH7

• Entry DOI: 10.2210/pdb4ph7/pdb
• Related: 3SPW
• Descriptor: Oxysterol-binding protein homolog 6, (2R)-1-{[(R)-hydroxy{[(1R,2R,3R,4R,5S,6R)-2,3,5,6-tetrahydroxy-4-(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}-3-(octadecanoyloxy)propan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate (3 entities in total)
• Functional Keywords: transport protein, osh proteins phosphatidylinositol phosphate lipid transport, lipid transport
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Endoplasmic reticulum membrane : Q02201
• Total number of polymer chains: 4
• Total formula weight: 211104.51

Authors

Delfosse, V.,Moser von Filseck, J.,Antonny, B.,Bourguet, W.,Drin, G. (deposition date: 2014-05-05, release date: 2015-07-29, Last modification date: 2023-12-20)

Primary citation

Moser von Filseck, J.,Copic, A.,Delfosse, V.,Vanni, S.,Jackson, C.L.,Bourguet, W.,Drin, G.
INTRACELLULAR TRANSPORT. Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate.
Science, 349:432-436, 2015

PubMed Abstract: In eukaryotic cells, phosphatidylserine (PS) is synthesized in the endoplasmic reticulum (ER) but is highly enriched in the plasma membrane (PM), where it contributes negative charge and to specific recruitment of signaling proteins. This distribution relies on transport mechanisms whose nature remains elusive. Here, we found that the PS transporter Osh6p extracted phosphatidylinositol 4-phosphate (PI4P) and exchanged PS for PI4P between two membranes. We solved the crystal structure of Osh6p:PI4P complex and demonstrated that the transport of PS by Osh6p depends on PI4P recognition in vivo. Finally, we showed that the PI4P-phosphatase Sac1p, by maintaining a PI4P gradient at the ER/PM interface, drove PS transport. Thus, PS transport by oxysterol-binding protein-related protein (ORP)/oxysterol-binding homology (Osh) proteins is fueled by PI4P metabolism through PS/PI4P exchange cycles.

PubMed: 26206936
DOI: 10.1126/science.aab1346

Experimental method

X-RAY DIFFRACTION (2.55 Å)