Phosphatidylcholine transfer protein (PCTP) also known as StAR-related lipid transfer domain protein 2 (STARD2) is a specific intracellular phospholipid

Phospholipid

Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

 binding protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that can transfer phosphatidylcholine

Phosphatidylcholine

Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...

 between different membranes in the cytosol

Cytosol

The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

.

In humans, phosphatidylcholine transfer protein is encoded by the PCTP gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Function

PCTP transfers phosphatidylcholine molecules between membranes in vitro

In vitro

In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

. Further studies found that sensitivity to phosphatidylcholine levels causes PCTP to interact with select enzymes, promoting their activation. PCTP stimulates the acyl-CoA thioesterase

Thioesterase

Thioesterases are enzymes which belong to the Esterase family. Esterases, in turn, are one type of the several hydrolases known.Thioesterases exhibit Esterase activity specifically at a thiol group.Thioesterases or thiolester hydrolases are identified as members of E.C.3.1.2.-Examples:Acetyl-coA...

 activity of thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (ACOT13) and the activity of homeodomain transcription factor paired box gene 3 (PAX3

PAX3

PAX3 is a gene that belongs to the paired box family of transcription factors. This gene was formerly known as splotch. PAX3 has been identified with ear, eye and facial development. Mutations in it can cause Waardenburg syndrome types 1 and 3...

). Protein kinase C phosphorylation promotes localization of PCTP to the mitochondrion where it may activate Them2.

Structure

This soluble protein is 214 amino acids long. It is almost entirely composed of a StAR-related transfer domain

StAR-related transfer domain

START is a lipid-binding domain in StAR, HD-ZIP and signalling proteins. The archetypical domain is found in StAR , a mitochondrial protein that is synthesized in steroid-producing cells. StAR and initiates steroid production by mediating the delivery of cholesterol to the first enzyme in...

 (START). X-ray crystallography

X-ray crystallography

X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...

 shows that this domain forms a pocket that can bind a single molecule

Molecule

A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

 of phosphatidylcholine.

This protein also founds the StarD2 subfamily of proteins. This subfamily consists of PCTP, StarD7

STARD7

StAR-related lipid transfer domain protein 7 or gestational trophoblastic tumor gene-1 is a lipid transporter that specifically binds and transports phosphatidylcholine between membranes.-Function and tissue distribution :...

, StarD10

STARD10

StAR-related lipid transfer protein 10 or PCTP-like protein is a lipid transfer protein that in humans is encoded by the STARD10 gene. The protein derives its name from the fact that the molecule contains a START domain. As part of the StarD2 subfamily, StarD10 can transport the lipids...

 and collagen type IV alpha-3-binding protein

COL4A3BP

Collagen type IV alpha-3-binding protein, ceramide transfer protein or StAR-related lipid transfer protein 11 is a protein that in humans is encoded by the COL4A3BP gene. The protein contains a pleckstrin homology domain at its amino terminus and a START domain towards the end of the molecule...

 or StarD11, all of which bind phosphatidylcholine except for StarD11 which prefers ceramide

Ceramide

Ceramides are a family of lipid molecules. A ceramide is composed of sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of cells. They are one of the component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer...

.

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

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

 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

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 and free fatty acid levels.