Oxysterol-binding protein

Oxysterol-binding protein
Crystallographic structure of the oxysterol-binding protein (rainbow color cartoon, N-terminus = blue, C-terminus = red) bound to 7-hydroxycholesterol (stick diagram, carbon = white, oxygen = red).[1]
Identifiers
SymbolOxysterol_BP
PfamPF01237
InterProIPR000648
PROSITEPDOC00774
OPM superfamily164
OPM protein1zi7
Membranome484
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

The oxysterol-binding protein (OSBP)-related proteins (ORPs) are a family of lipid transfer proteins (LTPs). Concretely, they constitute a family of sterol and phosphoinositide binding and transfer proteins in eukaryotes[2] that are conserved from yeast to humans. They are lipid-binding proteins implicated in many cellular processes related with oxysterol, including signaling, vesicular trafficking, lipid metabolism, and nonvesicular sterol transport.

In yeast cells, some ORPs might function as sterol or lipid transporters though yeast strains lacking ORPs do not have significant defects in sterol transport between the endoplasmic reticulum and the plasma membrane.[3] Although sterol transfer is proposed to occur at regions where organelle membranes are closely apposed, disruption of endoplasmic reticulum-plasma membrane contact sites do not have major effects on sterol transfer, though phospholipid homeostasis is perturbed.[4] Various ORPs confine at membrane contacts sites (MCS), where endoplasmic reticulum (ER) is apposed with other organelle limiting membranes. Yeast ORPs also participate in vesicular trafficking, in which they affect Sec14-dependent Golgi vesicle biogenesis[5] and, later in post-Golgi exocytosis, they affect exocyst complex-dependent vesicle tethering to the plasma membrane.[6] In mammalian cells, some ORPs function as sterol sensors that regulate the assembly of protein complexes in response to changes in cholesterol levels.[7] By that means, ORPs most likely affect organelle membrane lipid compositions, with impacts on signaling and vesicle transport, but also cellular lipid metabolism.[8]

Oxysterol is a cholesterol metabolite that can be produced through enzymatic or radical processes. Oxysterols, that are the 27-carbon products of cholesterol oxidation by both enzymic and non-enzymic mechanisms, constitute a large family of lipids involved in a plethora of physiological processes. Studies identifying the specific cellular targets of oxysterol indicate that several oxysterols may be regulators of cellular lipid metabolism via control of gene transcription. In addition, they were shown to be involved in other processes such as immune regulatory functions and brain homeostasis.[9][10]

  1. ^ PDB: 1ZHT​; Im YJ, Raychaudhuri S, Prinz WA, Hurley JH (September 2005). "Structural mechanism for sterol sensing and transport by OSBP-related proteins". Nature. 437 (7055): 154–8. Bibcode:2005Natur.437..154I. doi:10.1038/nature03923. PMC 1431608. PMID 16136145.
  2. ^ Weber-Boyvat M, Zhong W, Yan D, Olkkonen VM (July 2013). "Oxysterol-binding proteins: functions in cell regulation beyond lipid metabolism". Biochemical Pharmacology. 86 (1): 89–95. doi:10.1016/j.bcp.2013.02.016. PMID 23428468.
  3. ^ Georgiev, AG (2011). "Osh proteins regulate membrane sterol organization but are not required for sterol movement between the ER and PM". Traffic. 12 (10): 1341–55. doi:10.1111/j.1600-0854.2011.01234.x. PMC 3171641. PMID 21689253.
  4. ^ Quon, E (2018). "Endoplasmic reticulum-plasma membrane contact sites integrate sterol and phospholipid regulation". PLOS Biology. 16 (5): e2003864. doi:10.1371/journal.pbio.2003864. PMC 5983861. PMID 29782498.
  5. ^ Li, X (April 2002). "Analysis of oxysterol binding protein homologue Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex". J. Cell Biol. 157 (1): 63–77. doi:10.1083/jcb.200201037. PMC 2173257. PMID 11916983.
  6. ^ Alfaro, G (2011). "The sterol-binding protein Kes1/Osh4p is a regulator of polarized exocytosis". Traffic. 12 (11): 1521–36. doi:10.1111/j.1600-0854.2011.01265.x. PMID 21819498.
  7. ^ Raychaudhuri S, Prinz WA (10 November 2010). "The diverse functions of oxysterol-binding proteins". Annual Review of Cell and Developmental Biology. 26: 157–77. doi:10.1146/annurev.cellbio.042308.113334. PMC 3478074. PMID 19575662.
  8. ^ Weber-Boyvat M, Zhong W, Yan D, Olkkonen VM (July 2013). "Oxysterol-binding proteins: functions in cell regulation beyond lipid metabolism". Biochemical Pharmacology. 86 (1): 89–95. doi:10.1016/j.bcp.2013.02.016. PMID 23428468.
  9. ^ Mutemberezi V, Guillemot-Legris O, Muccioli GG (October 2016). "Oxysterols: From cholesterol metabolites to key mediators". Progress in Lipid Research. 64: 152–169. doi:10.1016/j.plipres.2016.09.002. PMID 27687912.
  10. ^ van Reyk DM, Brown AJ, Hult'en LM, Dean RT, Jessup W (1 January 2006). "Oxysterols in biological systems: sources, metabolism and pathophysiological relevance". Redox Report. 11 (6): 255–62. doi:10.1179/135100006X155003. PMID 17207307.