Emerging roles of the oxysterol-binding protein family in metabolism, transport, and signaling.
OSBP (oxysterol-binding protein) and ORPs (OSBP-related proteins) constitute an enigmatic eukaryotic protein family that is united by a signature domain that binds oxysterols, sterols, and possibly other hydrophobic ligands. The human genome contains 12 OSBP/ORP family members genes, while that of the budding yeast Saccharomyces cerevisiae encodes seven OSBP homologues (Osh). Of these, Osh4 (also referred to as Kes1) has been the most widely studied to date. Recently, three-dimensional crystal structures of Osh4 with and without sterols bound within the core of the protein were determined. The core consists of 19 anti-parallel beta-sheets that form a near-complete beta-barrel. Recent work has suggested that Osh proteins facilitate the non-vesicular transport of sterols in vivo and in vitro, while other evidence supports a role for Osh proteins in the regulation of vesicular transport and lipid metabolism. This article will review recent advances in the study of ORP/Osh proteins and will discuss future research issues regarding the ORP/Osh family.
Fairn
G D
GD
Department of Pediatrics, Atlantic Research Centre, Dalhousie University, B3H 4H7, Nova Scotia, Canada.
McMaster
C R
CR
D000818:Animals; D001692:Biological Transport; D006801:Humans; D050356:Lipid Metabolism; D011485:Protein Binding; D011987:Receptors, Steroid / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D000098825:Oxysterol Binding Proteins
D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; D000098825:Oxysterol Binding Proteins