The CFTR gene encodes a protein in cell membranes in epithelial tissues and affects multiple organ systems in the human body. Mutations in the CFTR gene cause dysfunctional regulation of cell electrolytes and water content.
What effect does the mutated CFTR channel have on the cell?
If the CFTR gene has a nonsense mutation, the protein-building instructions contain an early stop signal that causes the production of the CFTR protein to stop prematurely. Therefore, the cell begins to build the CFTR protein normally until it reaches the early stop signal.
How does CFTR open and close?
Control of CFTR activity is by ATP interactions with the NBDs that trigger a switch between “open” and “closed” conformations of the TMDs. The structural basis of this conformational change is not currently known.
Where is the CFTR channel?
This protein is a channel that sits on the surface of cells and transports chloride and other molecules, such as bicarbonate. The gene that encodes the CFTR protein, which is also called CFTR, is located on chromosome 7.
What is the mechanism of cystic fibrosis?
Cystic fibrosis is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein is responsible for regulating the flow of salt and fluids in and out of the cells in different parts of the body.
What type of channel is CFTR?
Cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-gated anion channel with two remarkable distinctions. First, it is the only ATP-binding cassette (ABC) transporter that is known to be an ion channel—almost all others function as transport ATPases.
What is the CFTR protein and what is its function?
The CFTR protein is mainly known as a Cl− channel of the exocrine glands that interacts with other ions channels and is essential for the osmotic balance of the mucus and its viscosity. As shown in Figure 2, the CFTR plays a major role in electrolyte and fluid secretion and absorption.
Which types of cells are affected in cystic fibrosis and why?
CF affects a cell protein called CFTR (cystic fibrosis transmembrane regulator). CFTR controls the flow of water and certain salts in and out of the body’s cells. As the movement of salt and water in and out of cells is changed, the mucus that many cells normally make gets thicker.
How does CFTR use ATP?
Like other ABC transporters, CFTR uses ATP binding to its two nucleotide binding domains (NBDs) to drive conformational rearrangements of its transmembrane domains (2, 3). CFTR channel opening is linked to ATP binding to each of two sites at the interface of an NBD1-NBD2 dimer (2, 3).
Is CFTR channel active transport?
Among human ABC proteins, CFTR is thought to be unique in that it has no active transport function, but instead acts as a phosphorylation-regulated, ATP-gated anion channel [5. The ABC protein turned chloride channel whose failure causes cystic fibrosis.
What kind of transport does the CFTR protein do active or passive?
The cystic fibrosis transmembrane conductance regulator (CFTR) is a channel/enzyme which mediates passive diffusion of chloride and bicarbonate through epithelial cell membranes.
Is CFTR in all cells?
CFTR is not only present in the cell membrane where it transports chloride ions and small neutral amino acids [117] and regulates other ion channels, it is also present in intracellular membranes.
Which organelle is affected by cystic fibrosis?
In most kids with cystic fibrosis, says Balch, the CFTR protein gets stuck inside the cells in a cell organelle known as the endoplasmic reticulum—a convoluted membranous sac within the cell where the synthesis of proteins like CFTR and other vital cell functions take place.
What causes cystic fibrosis at the cellular level?
Mutations in a gene called the CFTR (cystic fibrosis conductance transmembrane regulator) gene cause CF. The CFTR mutations causes changes in the body’s cell’s electrolyte transport system. Electrolytes are substances in blood that are critical to cell function.
What is the major problem at the cellular level in cystic fibrosis?
In people with CF, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the CFTR protein to become dysfunctional. When the protein is not working correctly, it’s unable to help move chloride — a component of salt — to the cell surface.
Is CFTR ATP dependent?
CFTR is a member of the ATP-binding cassette (ABC) family of membrane transport proteins, most members of which function as ATP-dependent pumps. CFTR is unique among human ABC proteins in functioning not as a pump, but as an ion channel.
What is CFTR protein structure?
CFTR is a single polypeptide containing an N-terminal lasso motif, two transmembrane domains (TMDs), and two nucleotide-binding domains (NBDs) (Fig. 1A). Distinct from other ABC transporters, CFTR also contains an ∼200-residue cytoplasmic regulatory (R) domain that regulates the activity of CFTR (Fig.
Is CFTR an ATPase?
It is a multidomain membrane protein, which utilizes ATP to regulate the flux of its substrate through the membrane. CFTR is distinct in that it functions as a channel and it possesses a unique regulatory R domain. There has been significant progress in understanding the molecular basis for CFTR activity as an ATPase.
What type of transporter best describes the CFTR protein?
CFTR belongs to the large ABC (ATP-binding cassette) transporter superfamily, of which most members are ATP-hydrolyzing pumps. CFTR is the sole ABC protein known to function as an ion channel.
How does cystic fibrosis affect cell membrane?
Cystic fibrosis The resulting abnormal channel breaks down shortly after it is made, so it never reaches the cell membrane to transport chloride ions. Disease-causing mutations in the CFTR gene alter the production, structure, or stability of the chloride channel.
How does cystic fibrosis affect biological processes?
In people with cystic fibrosis, the body produces mucus that is abnormally thick and sticky. This abnormal mucus can clog the airways , leading to severe problems with breathing and bacterial infections in the lungs. These infections cause chronic coughing, wheezing, and inflammation.
Why is the mucus thick in cystic fibrosis?
In people with cystic fibrosis, mucus is dehydrated, becoming so thick and sticky that the cilia are unable to propel mucus out of the lungs. As a result, the mucus clogs the airways. The largest airway is the trachea between the throat and the lungs. It branches into smaller airways in the lungs called bronchi.
What domain of CFTR is primarily targeted for phosphorylation?
Although the majority of the canonical phosphorylation sites are located within the R domain of CFTR, an additional residue (S422) in the RI region plays a key regulatory function (Lewis et al., 2004).
How big is the CFTR gene?
CFTR gene is localized on the long arm of chromosome 7 (7q21-34), spanning approximately 190 kb of genomic DNA. The gene consists of 27 exons and encodes a mature mRNA transcript of 6.5 kb that is translated into a 1480 amino acid protein (3).
How is the CFTR protein regulated?
The anion-selective pore of the CFTR protein is formed by its two transmembrane domains (TMDs) and regulated by its cytosolic domains: two nucleotide binding domains (NBDs) and a regulatory (R) domain.