The roles of the human lipid-binding proteins ORP9S and ORP10S in vesicular transport

2005 ◽  
Vol 83 (5) ◽  
pp. 631-636 ◽  
Author(s):  
Gregory D Fairn ◽  
Christopher R McMaster
Keyword(s):  
Binding Protein ◽  
Vesicular Transport ◽  
Lipid Binding ◽  
Yeast Cells ◽  
Phospholipid Transfer Protein ◽  
Related Protein ◽  
Oxysterol Binding Protein ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Lipid Binding Proteins

Inactivation of the yeast oxysterol binding protein related protein (ORP) family member Kes1p allows yeast cells to survive in the absence of Sec14p, a phospholipid transfer protein required for cell viability because of the role it plays in transporting vesicles from the Golgi. We expressed human ORP9S and ORP10S in yeast lacking Sec14p and Kes1p function, and found that ORP9S completely complemented Kes1p function, whereas ORP10S possessed only a weak ability to replace Kes1p function. Purified ORP9S protein bound several phosphoinositides, whereas ORP10 bound specifically to phosphatidylinositol 3-phosphate. The combined evidence demonstrates that only a subset of human ORP proteins can function as negative regulators of Golgi-derived vesicular transport.Key words: phospholipid, Saccharomyces cerevisiae, Golgi, vesicular transport, oxysterol binding protein related protein.

Bioinformatics of the TULIP domain superfamily

2011 ◽  
Vol 39 (4) ◽  
pp. 1033-1038 ◽  
Author(s):  
Klaus O. Kopec ◽  
Vikram Alva ◽  
Andrei N. Lupas
Keyword(s):  
Binding Protein ◽  
Lipid Binding ◽  
Phospholipid Transfer Protein ◽  
Hypothetical Proteins ◽  
Hormone Binding ◽  
Lipopolysaccharide Binding Protein ◽  
Transfer Protein ◽  
Unicellular Eukaryotes ◽  
Phospholipid Transfer ◽  
Lipopolysaccharide Binding

Proteins of the BPI (bactericidal/permeability-increasing protein)-like family contain either one or two tandem copies of a fold that usually provides a tubular cavity for the binding of lipids. Bioinformatic analyses show that, in addition to its known members, which include BPI, LBP [LPS (lipopolysaccharide)-binding protein)], CETP (cholesteryl ester-transfer protein), PLTP (phospholipid-transfer protein) and PLUNC (palate, lung and nasal epithelium clone) protein, this family also includes other, more divergent groups containing hypothetical proteins from fungi, nematodes and deep-branching unicellular eukaryotes. More distantly, BPI-like proteins are related to a family of arthropod proteins that includes hormone-binding proteins (Takeout-like; previously described to adopt a BPI-like fold), allergens and several groups of uncharacterized proteins. At even greater evolutionary distance, BPI-like proteins are homologous with the SMP (synaptotagmin-like, mitochondrial and lipid-binding protein) domains, which are found in proteins associated with eukaryotic membrane processes. In particular, SMP domain-containing proteins of yeast form the ERMES [ER (endoplasmic reticulum)-mitochondria encounter structure], required for efficient phospholipid exchange between these organelles. This suggests that SMP domains themselves bind lipids and mediate their exchange between heterologous membranes. The most distant group of homologues we detected consists of uncharacterized animal proteins annotated as TM (transmembrane) 24. We propose to group these families together into one superfamily that we term as the TULIP (tubular lipid-binding) domain superfamily.

scholarly journals A role for oxysterol-binding protein–related protein 5 in endosomal cholesterol trafficking

2011 ◽  
Vol 192 (1) ◽  
pp. 121-135 ◽  
Author(s):  
Ximing Du ◽  
Jaspal Kumar ◽  
Charles Ferguson ◽  
Timothy A. Schulz ◽  
Yan Shan Ong ◽  
...  
Keyword(s):  
Binding Protein ◽  
Lipid Binding ◽  
Cholesterol Trafficking ◽  
Cholesterol Accumulation ◽  
Oxysterol Binding Protein ◽  
Late Endosomes ◽  
Evolutionarily Conserved ◽  
Niemann Pick ◽  
Related Proteins ◽  
Lipid Binding Proteins

Oxysterol-binding protein (OSBP) and its related proteins (ORPs) constitute a large and evolutionarily conserved family of lipid-binding proteins that target organelle membranes to mediate sterol signaling and/or transport. Here we characterize ORP5, a tail-anchored ORP protein that localizes to the endoplasmic reticulum. Knocking down ORP5 causes cholesterol accumulation in late endosomes and lysosomes, which is reminiscent of the cholesterol trafficking defect in Niemann Pick C (NPC) fibroblasts. Cholesterol appears to accumulate in the limiting membranes of endosomal compartments in ORP5-depleted cells, whereas depletion of NPC1 or both ORP5 and NPC1 results in luminal accumulation of cholesterol. Moreover, trans-Golgi resident proteins mislocalize to endosomal compartments upon ORP5 depletion, which depends on a functional NPC1. Our results establish the first link between NPC1 and a cytoplasmic sterol carrier, and suggest that ORP5 may cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes.

scholarly journals Lipopolysaccharide Is Transferred from High-Density to Low-Density Lipoproteins by Lipopolysaccharide-Binding Protein and Phospholipid Transfer Protein

2005 ◽  
Vol 73 (4) ◽  
pp. 2321-2326 ◽  
Author(s):  
J. H. M. Levels ◽  
J. A. Marquart ◽  
P. R. Abraham ◽  
A. E. van den Ende ◽  
H. O. F. Molhuizen ◽  
...  
Keyword(s):  
Acute Phase ◽  
Binding Protein ◽  
Low Density Lipoproteins ◽  
High Density ◽  
Phospholipid Transfer Protein ◽  
Low Density ◽  
Lipoprotein Subclasses ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Dose Dependent

ABSTRACT Lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria, is a potent endotoxin that triggers cytokine-mediated systemic inflammatory responses in the host. Plasma lipoproteins are capable of LPS sequestration, thereby attenuating the host response to infection, but ensuing dyslipidemia severely compromises this host defense mechanism. We have recently reported that Escherichia coli J5 and Re595 LPS chemotypes that contain relatively short O-antigen polysaccharide side chains are efficiently redistributed from high-density lipoproteins (HDL) to other lipoprotein subclasses in normal human whole blood (ex vivo). In this study, we examined the role of the acute-phase proteins LPS-binding protein (LBP) and phospholipid transfer protein (PLTP) in this process. By the use of isolated HDL containing fluorescent J5 LPS, the redistribution of endotoxin among the major lipoprotein subclasses in a model system was determined by gel permeation chromatography. The kinetics of LPS and lipid particle interactions were determined by using Biacore analysis. LBP and PLTP were found to transfer LPS from HDL predominantly to low-density lipoproteins (LDL), in a time- and dose-dependent manner, to induce remodeling of HDL into two subpopulations as a consequence of the LPS transfer and to enhance the steady-state association of LDL with HDL in a dose-dependent fashion. The presence of LPS on HDL further enhanced LBP-dependent interactions of LDL with HDL and increased the stability of the HDL-LDL complexes. We postulate that HDL remodeling induced by LBP- and PLTP-mediated LPS transfer may contribute to the plasma lipoprotein dyslipidemia characteristic of the acute-phase response to infection.

scholarly journals Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein–related proteins and phosphoinositides

2006 ◽  
Vol 173 (1) ◽  
pp. 107-119 ◽  
Author(s):  
Sumana Raychaudhuri ◽  
Young Jun Im ◽  
James H. Hurley ◽  
William A. Prinz
Keyword(s):  
Plasma Membrane ◽  
Binding Protein ◽  
Large Family ◽  
Lipid Binding ◽  
Oxysterol Binding Protein ◽  
Sterol Transport ◽  
Cellular Compartments ◽  
Related Proteins ◽  
Lipid Binding Proteins

Sterols are moved between cellular membranes by nonvesicular pathways whose functions are poorly understood. In yeast, one such pathway transfers sterols from the plasma membrane (PM) to the endoplasmic reticulum (ER). We show that this transport requires oxysterol-binding protein (OSBP)–related proteins (ORPs), which are a large family of conserved lipid-binding proteins. We demonstrate that a representative member of this family, Osh4p/Kes1p, specifically facilitates the nonvesicular transfer of cholesterol and ergosterol between membranes in vitro. In addition, Osh4p transfers sterols more rapidly between membranes containing phosphoinositides (PIPs), suggesting that PIPs regulate sterol transport by ORPs. We confirmed this by showing that PM to ER sterol transport slows dramatically in mutants with conditional defects in PIP biosynthesis. Our findings argue that ORPs move sterols among cellular compartments and that sterol transport and intracellular distribution are regulated by PIPs.

scholarly journals Lipopolysaccharide-Binding Protein and Phospholipid Transfer Protein Release Lipopolysaccharides from Gram-Negative Bacterial Membranes

2000 ◽  
Vol 68 (5) ◽  
pp. 2410-2417 ◽  
Author(s):  
C. J. Vesy ◽  
R. L. Kitchens ◽  
G. Wolfbauer ◽  
J. J. Albers ◽  
R. S. Munford
Keyword(s):  
Human Serum ◽  
Binding Protein ◽  
Normal Human Serum ◽  
High Density Lipoproteins ◽  
Phospholipid Transfer Protein ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Normal Human

ABSTRACT Although animals mobilize their innate defenses against gram-negative bacteria when they sense the lipid A moiety of bacterial lipopolysaccharide (LPS), excessive responses to this conserved bacterial molecule can be harmful. Of the known ways for decreasing the stimulatory potency of LPS in blood, the binding and neutralization of LPS by plasma lipoproteins is most prominent. The mechanisms by which host lipoproteins take up the native LPS that is found in bacterial membranes are poorly understood, however, since almost all studies of host-LPS interactions have used purified LPS aggregates. Using nativeSalmonella enterica serovar Typhimurium outer membrane fragments (blebs) that contained 3H-labeled lipopolysaccharide (LPS) and 35S-labeled protein, we found that two human plasma proteins, LPS-binding protein (LBP) and phospholipid transfer protein (PLTP), can extract [3H]LPS from bacterial membranes and transfer it to human high-density lipoproteins (HDL). Soluble CD14 (sCD14) did not release LPS from blebs yet could facilitate LBP-mediated LPS transfer to HDL. LBP, but not PLTP, also promoted the activation of human monocytes by bleb-derived LPS. Whereas depleting or neutralizing LBP significantly reduced LPS transfer from blebs to lipoproteins in normal human serum, neutralizing serum PLTP had no demonstrable effect. Of the known lipid transfer proteins, LBP is thus most able to transfer LPS from bacterial membranes to the lipoproteins in normal human serum.

scholarly journals Identification and assessment of the role of a nominal phospholipid binding region of ORP1S (oxysterol-binding-protein-related protein 1 short) in the regulation of vesicular transport

2005 ◽  
Vol 387 (3) ◽  
pp. 889-896 ◽  
Author(s):  
Gregory D. FAIRN ◽  
Christopher R. McMASTER
Keyword(s):  
Binding Protein ◽  
Vesicular Transport ◽  
Lipid Binding ◽  
Binding Domain ◽  
Negative Regulator ◽  
Carboxypeptidase Y ◽  
Binding Region ◽  
Phospholipid Binding ◽  
Oxysterol Binding Protein

The ORPs (oxysterol-binding-protein-related proteins) constitute an enigmatic family of intracellular lipid receptors that are related through a shared lipid binding domain. Emerging evidence suggests that ORPs relate lipid metabolism to membrane transport. Current data imply that the yeast ORP Kes1p is a negative regulator of Golgi-derived vesicular transport mediated by the essential phosphatidylinositol/phosphatidylcholine transfer protein Sec14p. Inactivation of Kes1p function allows restoration of growth and vesicular transport in cells lacking Sec14p function, and Kes1p function in this regard can be complemented by human ORP1S (ORP1 short). Recent studies have determined that Kes1p and ORP1S both bind phospholipids as ligands. To explore the function of distinct linear segments of ORP1S in phospholipid binding and vesicular transport regulation, we generated a series of 15 open reading frames coding for diagnostic regions within ORP1S. Purified versions of these ORP1S deletion proteins were characterized in vitro, and allowed the identification of a nominal phospholipid binding region. The in vitro analysis was interpreted in the context of in vivo growth and vesicle transport assays for members of the ORP1S deletion set. The results determined that the phospholipid binding domain per se was insufficient for inhibition of vesicular transport by ORP1S, and that transport of carboxypeptidase Y and invertase from the Golgi may be regulated differentially by specific regions of ORP1S/Kes1p.

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