Biology:Phosphatidylcholine transfer protein

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Short description: Intracellular phospholipid binding protein


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Phosphatidylcholine transfer protein (PCTP), also known as StAR-related lipid transfer domain protein 2 (STARD2), is a specific intracellular phospholipid binding protein that can transfer phosphatidylcholine between different membranes in the cytosol.[1][2]

In humans, phosphatidylcholine transfer protein is encoded by the PCTP gene.[3][4]

Function

PCTP transfers phosphatidylcholine molecules between membranes in vitro.[2] Further studies found that sensitivity to phosphatidylcholine levels causes PCTP to interact with select enzymes, promoting their activation. PCTP stimulates the acyl-CoA thioesterase activity of thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (ACOT13) and the activity of homeodomain transcription factor paired box gene 3 (PAX3).[5] Protein kinase C phosphorylation promotes localization of PCTP to the mitochondrion where it may activate Them2.[6]

Structure

This soluble protein is 214 amino acids long. It is almost entirely composed of a StAR-related transfer domain (START). X-ray crystallography shows that this domain forms a pocket that can bind a single molecule of phosphatidylcholine.[7]

This protein also founds the StarD2 subfamily of proteins. This subfamily consists of PCTP, StarD7, StarD10 and collagen type IV alpha-3-binding protein or StarD11, all of which bind phosphatidylcholine except for StarD11 which prefers ceramide.

Tissue distribution and pathology

PCTP is produced in all tissues in the body at various levels. The protein is expressed at high levels in tissues engaged in high metabolism, notably including the liver and macrophages.[2][8]

No human patients with defects in PCTP have been described to date. Mice lacking PCTP exhibit a resistance to atherosclerosis linked to changes in plasma lipid levels and changes in body weight linked to the level of brown fat use of fatty acids and Them2 activity.[9][10] Loss of PCTP in fasting mice alters the sensitivity of the liver to insulin, reducing glucose and free fatty acid levels.[11]

References

  1. ↑ "Phospholipid transfer proteins in rat lung. Identification of a protein specific for phosphatidylglycerol". J. Biol. Chem. 255 (13): 6011–3. July 1980. doi:10.1016/S0021-9258(18)43688-5. PMID 7391000. 
  2. ↑ 2.0 2.1 2.2 Wirtz KW (July 1991). "Phospholipid transfer proteins.". Annu. Rev. Biochem. 60 (13): 73–99. doi:10.1146/annurev.bi.60.070191.000445. PMID 1883207. 
  3. ↑ "Entrez Gene: phosphatidylcholine transfer protein". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=58488. 
  4. ↑ "Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11501–6. September 1999. doi:10.1073/pnas.96.20.11501. PMID 10500206. Bibcode: 1999PNAS...9611501V. 
  5. ↑ "Interacting proteins dictate function of the minimal START domain phosphatidylcholine transfer protein/StarD2". J. Biol. Chem. 282 (42): 30728–36. October 2007. doi:10.1074/jbc.M703745200. PMID 17704541. 
  6. ↑ "Clofibrate-induced relocation of phosphatidylcholine transfer protein to mitochondria in endothelial cells". Exp. Cell Res. 274 (1): 100–11. March 2002. doi:10.1006/excr.2001.5460. PMID 11855861. 
  7. ↑ "Structure of human phosphatidylcholine transfer protein in complex with its ligand". Nature Structural & Molecular Biology 9 (7): 507–11. July 2002. doi:10.1038/nsb812. PMID 12055623. 
  8. ↑ "Decreased lipid efflux and increased susceptibility to cholesterol-induced apoptosis in macrophages lacking phosphatidylcholine transfer protein". Biochem. J. 388 (Pt 1): 57–63. May 2005. doi:10.1042/BJ20041899. PMID 15628972. 
  9. ↑ "Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E deficient mice". J. Lipid Res. 47 (11): 2400–7. 2006. doi:10.1194/jlr.M600277-JLR200. PMID 16940277. 
  10. ↑ "Mice lacking Pctp /StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue". J. Lipid Res. 50 (11): 2212–21. November 2009. doi:10.1194/jlr.M900013-JLR200. PMID 19502644. 
  11. ↑ "Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2". FASEB J. 22 (7): 2579–90. July 2008. doi:10.1096/fj.07-105395. PMID 18347010. 

External links

  • Overview of all the structural information available in the PDB for UniProt: Q9UKL6 (Phosphatidylcholine transfer protein) at the PDBe-KB.



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