phosphatidylcholine transfer protein#Structure
{{Short description|Intracellular phospholipid binding protein}}
{{Infobox_gene}}
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.{{cite journal |vauthors=van Golde LM, Oldenborg V, Post M, Batenburg JJ, Poorthuis BJ, Wirtz KW | title = Phospholipid transfer proteins in rat lung. Identification of a protein specific for phosphatidylglycerol | journal = J. Biol. Chem. | volume = 255| issue = 13| pages = 6011–3|date=July 1980 | doi = 10.1016/S0021-9258(18)43688-5 | pmid = 7391000 | doi-access = free }}{{cite journal | author = Wirtz KW | title = Phospholipid transfer proteins. | journal = Annu. Rev. Biochem. | volume = 60| issue = 13| pages = 73–99|date=July 1991 | pmid = 1883207 | doi = 10.1146/annurev.bi.60.070191.000445 }}
In humans, phosphatidylcholine transfer protein is encoded by the PCTP gene.{{cite web | title = Entrez Gene: phosphatidylcholine transfer protein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=58488}}{{cite journal |vauthors=van Helvoort A, de Brouwer A, Ottenhoff R, Brouwers JF, Wijnholds J, Beijnen JH, Rijneveld A, van der Poll T, van der Valk MA, Majoor D, Voorhout W, Wirtz KW, Elferink RP, Borst P | title = Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 20 | pages = 11501–6 |date=September 1999 | pmid = 10500206 | pmc = 18063 | doi = 10.1073/pnas.96.20.11501| bibcode = 1999PNAS...9611501V | doi-access = free }}
Function
PCTP transfers phosphatidylcholine molecules between membranes in vitro. 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).{{cite journal |vauthors=Kanno K, Wu MK, Agate DA, Fanelli BK, Wagle N, Scapa EF, Ukomadu C, Cohen DE | title = Interacting proteins dictate function of the minimal START domain phosphatidylcholine transfer protein/StarD2 | journal = J. Biol. Chem. | volume = 282 | issue = 42 | pages = 30728–36 |date=October 2007 | pmid = 17704541 | doi = 10.1074/jbc.M703745200 | doi-access = free }} Protein kinase C phosphorylation promotes localization of PCTP to the mitochondrion where it may activate Them2.{{cite journal |vauthors=de Brouwer AP, Westerman J, Kleinnijenhuis A, Bevers LE, Roelofsen B, Wirtz KW | title = Clofibrate-induced relocation of phosphatidylcholine transfer protein to mitochondria in endothelial cells | journal = Exp. Cell Res. | volume = 274 | issue = 1 | pages = 100–11 |date=March 2002 | pmid = 11855861 | doi = 10.1006/excr.2001.5460 | hdl = 1874/14384 | s2cid = 21938117 | hdl-access = free }}
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.{{cite journal |vauthors=Roderick SL, Chan WW, Agate DS, Olsen LR, Vetting MW, Rajashankar KR, Cohen DE | title = Structure of human phosphatidylcholine transfer protein in complex with its ligand | journal = Nature Structural & Molecular Biology | volume = 9 | issue = 7 | pages = 507–11 |date=July 2002 | pmid = 12055623 | doi = 10.1038/nsb812 | s2cid = 8208598 }}
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.{{cite journal |vauthors=Baez JM, Tabas I, Cohen DE | title = Decreased lipid efflux and increased susceptibility to cholesterol-induced apoptosis in macrophages lacking phosphatidylcholine transfer protein | journal = Biochem. J. | volume = 388 | issue = Pt 1 | pages = 57–63 |date=May 2005 | pmid = 15628972 | doi = 10.1042/BJ20041899| pmc=1186693}}
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.{{cite journal |vauthors=Wang WJ, Baez JM, Maurer R, Dansky HM, Cohen DE | title = Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E deficient mice | journal = J. Lipid Res. | volume = 47 | issue = 11 | pages = 2400–7 | year = 2006 | pmid = 16940277 | doi = 10.1194/jlr.M600277-JLR200 | doi-access = free }}{{cite journal |vauthors=Kang HW, Ribich S, Kim BW, Hagen SJ, Bianco AC, Cohen DE | title = Mice lacking Pctp /StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue | journal = J. Lipid Res. | volume = 50 | issue = 11 | pages = 2212–21 |date=November 2009 | pmid = 19502644 | doi = 10.1194/jlr.M900013-JLR200 |doi-access=free | pmc=2759827}} Loss of PCTP in fasting mice alters the sensitivity of the liver to insulin, reducing glucose and free fatty acid levels.{{cite journal |vauthors=Scapa EF, Pocai A, Wu MK, Gutierrez-Juarez R, Glenz L, Kanno K, Li H, Biddinger S, Jelicks LA, Rossetti L, Cohen DE | title = Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2 | journal = FASEB J. | volume = 22 | issue = 7 | pages = 2579–90 |date=July 2008 | pmid = 18347010 | doi = 10.1096/fj.07-105395 | doi-access = free | s2cid = 19224763 }}
References
{{Reflist}}
External links
- {{PDBe-KB2|Q9UKL6|Phosphatidylcholine transfer protein}}
{{PDB Gallery|geneid=58488}}