Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues |
| |
Authors: | Timothy A Schulz Mal-Gi Choi Sumana Raychaudhuri Jason A Mears Rodolfo Ghirlando Jenny E Hinshaw William A Prinz |
| |
Institution: | 1.Laboratory of Cell Biochemistry and Biology, and 2.Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 |
| |
Abstract: | Sterols are transferred between cellular membranes by vesicular and poorly understood nonvesicular pathways. Oxysterol-binding protein–related proteins (ORPs) have been implicated in sterol sensing and nonvesicular transport. In this study, we show that yeast ORPs use a novel mechanism that allows regulated sterol transfer between closely apposed membranes, such as organelle contact sites. We find that the core lipid-binding domain found in all ORPs can simultaneously bind two membranes. Using Osh4p/Kes1p as a representative ORP, we show that ORPs have at least two membrane-binding surfaces; one near the mouth of the sterol-binding pocket and a distal site that can bind a second membrane. The distal site is required for the protein to function in cells and, remarkably, regulates the rate at which Osh4p extracts and delivers sterols in a phosphoinositide-dependent manner. Together, these findings suggest a new model of how ORPs could sense and regulate the lipid composition of adjacent membranes. |
| |
Keywords: | |
|
|