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The OSBP-related proteins: a novel protein family involved in vesicle transport,cellular lipid metabolism,and cell signalling
Authors:Markku Lehto  Vesa M Olkkonen
Institution:Department of Molecular Medicine, National Public Health Institute, Biomedicum, P.O. Box 104, Haartmaninkatu 8, FIN-00251 Helsinki, Finland
Abstract:Proteins/genes showing high sequence homology to the mammalian oxysterol binding protein (OSBP) have been identified in a variety of eukaryotic organisms from yeast to man. The unifying feature of the gene products denoted as OSBP-related proteins (ORPs) is the presence of an OSBP-type ligand binding (LB) domain. The LB domains of OSBP and its closest homologue bind oxysterols, while data on certain other family members suggest interaction with phospholipids. Many ORPs also have a pleckstrin homology (PH) domain in the amino-terminal region. The PH domains of the family members studied in detail are known to interact with membrane phosphoinositides and play an important role in the intracellular targeting of the proteins. It is plausible that the ORPs constitute a regulatory apparatus that senses the status of specific lipid ligands in membranes, using the PH and/or LB domains, and mediates information to yet poorly known downstream machineries. Functional studies carried out on the ORP proteins in different organisms indicate roles of the gene family in diverse cellular processes including control of lipid metabolism, regulation of vesicle transport, and cell signalling events.
Keywords:Cell signalling  Cholesterol metabolism  Membrane trafficking  ORP  Oxysterol binding protein  Pleckstrin homology domain  Protein family  ACAT  acyl-coenzyme A cholesterol acyltransferase  ARF  adenosinediphosphate ribosylation factor  CHO  Chinese hamster ovary (cell line)  ER  endoplasmic reticulum  GTPase  guanosinetriphosphatase  HMG-CoA  3-hydroxy-3-methylglutaryl coenzyme A  LB  ligand binding  LDL  low-density lipoprotein  25-OHC  25-hydroxycholesterol  ORP  OSBP-related protein  OSBP  oxysterol binding protein  Osh  (yeast) OSBP homologue  PC  phosphatidylcholine  PI  phosphatidylinositol  PI(4)P  phosphatidylinositol-4-phosphate  PH  pleckstrin homology  SREBP  sterol regulatory element binding protein  VSVG  vesicular stomatitis virus G protein
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