Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues
| Autor: | Sumana Raychaudhuri, Timothy A. Schulz, Rodolfo Ghirlando, Jason A. Mears, William A. Prinz, Mal Gi Choi, Jenny E. Hinshaw |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Receptors Steroid Saccharomyces cerevisiae Proteins Protein Conformation Membrane lipids Recombinant Fusion Proteins Biology Endoplasmic Reticulum Phosphatidylinositols Article Membrane Lipids Organelle OSBP Research Articles Binding Sites Endoplasmic reticulum fungi food and beverages Membrane Proteins Biological Transport Cell Biology Cell biology Protein Structure Tertiary Kinetics Sterols Membrane Membrane protein Oxysterol binding Liposomes Mutation lipids (amino acids peptides and proteins) Oxysterol-binding protein Carrier Proteins |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | The ORP lipid-binding domain can contact two membranes simultaneously to facilitate sterol extraction or delivery at one membrane in response to the lipid composition of the other. 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. |
| Databáze: | OpenAIRE |
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