Phosphatidylcholine Transfer Protein
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Phosphatidylcholine transfer protein (PCTP), also known as StAR-related lipid transfer domain protein 2 (STARD2), is a specific intracellular
phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
binding
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that can transfer
phosphatidylcholine Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup. They are a major component of biological membranes and can easily be obtained from a variety of readily available sources, such as egg yolk or soyb ...
between different membranes in the
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
. In humans, phosphatidylcholine transfer protein is encoded by the ''PCTP''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.


Function

PCTP transfers phosphatidylcholine molecules between membranes ''
in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
''. Further studies found that sensitivity to phosphatidylcholine levels causes PCTP to interact with select
enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
, 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 The PAX3 (paired box gene 3) gene encodes a member of the paired box or Pax genes, PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX ...
). Protein kinase C phosphorylation promotes localization of PCTP to the mitochondrion where it may activate Them2.


Structure

This soluble protein is 214
amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
long. It is almost entirely composed of a StAR-related transfer domain (START).
X-ray crystallography X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...
shows that this domain forms a pocket that can bind a single
molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
of phosphatidylcholine. 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 Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of Eukaryote, eukaryotic cells, since they are co ...
.


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. No human patients with defects in PCTP have been described to date. Mice lacking PCTP exhibit a resistance to
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
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. Loss of PCTP in fasting mice alters the sensitivity of the liver to insulin, reducing
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
and
free fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
levels.


References


External links

* {{PDB Gallery, geneid=58488 Genes on human chromosome 17 Water-soluble transporters