TY - JOUR
T1 - Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues
AU - Schulz, Timothy A.
AU - Choi, Mal Gi
AU - Raychaudhuri, Sumana
AU - Mears, Jason A.
AU - Ghirlando, Rodolfo
AU - Hinshaw, Jenny E.
AU - Prinz, William A.
PY - 2009/12/14
Y1 - 2009/12/14
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.200905007
DO - 10.1083/jcb.200905007
M3 - Article
C2 - 20008566
AN - SCOPUS:74049122402
SN - 0021-9525
VL - 187
SP - 889
EP - 903
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -