Disease relevance of PCTP

• Optimization of codon usage for bacterial protein translation increased expression of PC-TP from trace levels to >10% of the E. coli cytosolic protein mass [1].

High impact information on PCTP

• In mammalian cells, these insoluble molecules are transferred between membranes by a highly specific phosphatidylcholine transfer protein (PC-TP) belonging to the steroidogenic acute regulatory protein related transfer (START) domain superfamily of hydrophobic ligand-binding proteins [2].
• The protein levels and the immunohistochemical staining were decreased for MDR3 Pgp and PCTP in the liver [3].
• These studies have revealed that the phosphatidylinositol/phosphatidylcholine transfer protein, considered to mediate intracellular phospholipid transfer, is a critical component of the secretory pathway for proteins [4].
• PC-TP did not affect cellular phospholipid compositions, phosphatidylcholine contents, or phosphatidylcholine synthetic rates [5].
• Phosphatidylcholine transfer protein promotes apolipoprotein A-I-mediated lipid efflux in Chinese hamster ovary cells [5].

Chemical compound and disease context of PCTP

• To probe mechanisms for membrane interactions and phosphatidylcholine binding, we expressed recombinant human PC-TP in Escherichia coli using a synthetic gene [1].

Biological context of PCTP

• Computer-mediated homology search revealed that the deduced amino acid sequence had similarity to phosphatidylcholine transfer protein (PCTP) with a conserved StAR-related lipid transfer (START) domain extending between the amino acids 66 to 250 [6].
• We conclude that a major route for the turnover of plasma high density lipoprotein-phosphatidylcholine in the rat is independent of spontaneous lipid transfer, hydrolysis, and HDL particle uptake, and that it involves the activity of a plasma phosphatidylcholine transfer protein [7].
• High-level expression and mutagenesis of recombinant human phosphatidylcholine transfer protein using a synthetic gene: evidence for a C-terminal membrane binding domain [1].
• Moreover, they imply that 75% of the phosphatidylcholine transfer activity and more than 95% of the phosphatidylinositol and phosphatidylethanolamine transfer activities present in pH 5.1 supernatants of unfertilized oocytes may not be essential for toad embryo development [8].
• The kinetics of spin-labeled phosphatidylcholine transfer between vesicles and HDL particles exhibited a two-phase process, as seen by ESR spectroscopy [9].

Anatomical context of PCTP

• These findings suggest that a physiological function of PC-TP is to replenish the plasma membrane with phosphatidylcholines that are removed during pre-beta-HDL particle formation due to the activity of ATP-binding cassette A1 [5].
• Using stably transfected CHO cells, we explored the influence of PC-TP on apolipoprotein A-I- and high density lipoprotein 3 (HDL(3))-mediated lipid efflux [5].
• Phosphatidylcholine transfer activity in pH 5.1 supernatant of unfertilized oocytes was 8-fold higher than the activity found in female toad liver supernatant, but dropped steadily after fertilization [8].
• After 20 hr of development, at the stage of late blastula, the phosphatidylcholine transfer activity had dropped 4-fold [8].
• Isoelectric focusing of the platelet cytosol yielded phosphatidylinositol and phosphatidylcholine transfer activity at pH 5.6 and 5 [10].

Associations of PCTP with chemical compounds

• We have expressed, purified and crystallized recombinant human phosphatidylcholine transfer protein (PC-TP) and selenomethionyl PC-TP bound to dilinoleoyl phosphatidylcholine [11].
• This was in contrast to a progressive decline in the rate of phosphatidylcholine transfer with an increase in the cholesterol content [12].
• We conclude that triglyceride and cholesteryl ester compete for transfer and that the extent of transfer for each lipid is determined by its relative concentration in the donor particle, whereas phosphatidylcholine transfer is independent of triglyceride and cholesteryl ester transfer [13].

Other interactions of PCTP

• Both the HDL conversion and the phosphatidylcholine transfer activities of purified PLTP were effectively inhibited by rabbit anti-PLTP immunoglobulin G [14].
• The human and rat alpha TTPs show structural similarity with other apparently unrelated lipid-binding/transfer proteins, i.e. retinaldehyde-binding protein present in retina, and yeast SEC14 protein, which possesses phosphatidylinositol/phosphatidylcholine transfer activity [15].

Analytical, diagnostic and therapeutic context of PCTP

• Human phosphatidylcholine transfer protein: purification, crystallization and preliminary X-ray diffraction data [11].

References