3SPW

Structure of Osh4p/Kes1p in complex with phosphatidylinositol 4-phosphate

Summary for 3SPW

• Entry DOI: 10.2210/pdb3spw/pdb
• Related: 1ZHZ
• Descriptor: Protein KES1, (2R)-1-(heptadecanoyloxy)-3-{[(R)-hydroxy{[(1R,2R,3R,4R,5S,6R)-2,3,5,6-tetrahydroxy-4-(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate (3 entities in total)
• Functional Keywords: lipid binding protein, protein binding
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Total number of polymer chains: 2
• Total formula weight: 101310.21

Authors

Delfosse, V.,de Saint-Jean, M.,Douguet, D.,Antonny, B.,Drin, G.,Bourguet, W. (deposition date: 2011-07-04, release date: 2011-11-23, Last modification date: 2023-09-13)

Primary citation

de Saint-Jean, M.,Delfosse, V.,Douguet, D.,Chicanne, G.,Payrastre, B.,Bourguet, W.,Antonny, B.,Drin, G.
Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers.
J.Cell Biol., 195:965-978, 2011

PubMed Abstract: Osh/Orp proteins transport sterols between organelles and are involved in phosphoinositide metabolism. The link between these two aspects remains elusive. Using novel assays, we address the influence of membrane composition on the ability of Osh4p/Kes1p to extract, deliver, or transport dehydroergosterol (DHE). Surprisingly, phosphatidylinositol 4-phosphate (PI(4)P) specifically inhibited DHE extraction because PI(4)P was itself efficiently extracted by Osh4p. We solve the structure of the Osh4p-PI(4)P complex and reveal how Osh4p selectively substitutes PI(4)P for sterol. Last, we show that Osh4p quickly exchanges DHE for PI(4)P and, thereby, can transport these two lipids between membranes along opposite routes. These results suggest a model in which Osh4p transports sterol from the ER to late compartments pinpointed by PI(4)P and, in turn, transports PI(4)P backward. Coupled to PI(4)P metabolism, this transport cycle would create sterol gradients. Because the residues that recognize PI(4)P are conserved in Osh4p homologues, other Osh/Orp are potential sterol/phosphoinositol phosphate exchangers.

PubMed: 22162133
DOI: 10.1083/jcb.201104062

Experimental method

X-RAY DIFFRACTION (2.6 Å)