What is the structure of the CFTR protein?

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. 1A).

Does CFTR have tertiary structure?

Cystic fibrosis is caused by mutation in the CFTR protein. The deletion of phenylalanine at position 508 is crucial due to the position of this residue in the tertiary structure of the protein.

What is the secondary structure of CFTR?

These segments have a secondary structure which is largely α-helical in nature (2, 9). In the two MSDs, the segments are connected to form three traversing loops across the membrane, with little of the protein exposed extracellularly (4). However several important extracellular sites have been discovered.

What protein structure is affected by cystic fibrosis?

Cystic fibrosis occurs when the cystic fibrosis transmembrane conductance regulator (CFTR) protein is either not made correctly, or not made at all.

Is CFTR 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.

How is CFTR 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.

Does CFTR have a primary structure?

Identification of an ion channel-forming motif in the primary structure of CFTR, the cystic fibrosis chloride channel. CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell, 81: 1063-1073.

Is CFTR hydrophilic or hydrophobic?

CFTR is an apical plasma membrane chloride channel CFTR is composed of two repeated motifs, each of which consists of a hydrophobic membrane-spanning domain (MSD) containing six helices and a cytosolic hydrophilic region for binding with ATP (i.e., nucleotide binding domain, NBD)3 (Fig. 1).

Is CFTR tertiary or quaternary?

We conclude that, in addition to its role in Cl- transport, HI-NBD2 domain confers membrane stability of CFTR by consolidating its quaternary structure through interactions with HI-NBD1 region. Keywords: CFTR; Cystic fibrosis; Dimerization; Membrane stability; NBD2; Quaternary structure.

How does CFTR affect cystic fibrosis?

The cystic fibrosis transmembrane conductance regulator (CFTR) gene contains the instructions for making the CFTR protein. In people with CF, mutations in the CFTR gene cause the CFTR protein to malfunction, leading to a buildup of thick mucus.

What happens to the CFTR protein in cystic fibrosis?

Mutations in the CFTR gene cause the CFTR protein to malfunction or not be made at all, leading to a buildup of thick mucus, which in turn leads to persistent lung infections, destruction of the pancreas, and complications in other organs. Cystic fibrosis is an example of a recessive disease.

What type of transport is CFTR?

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.

It is a member of the ATP binding cassette (ABC) superfamily of proteins which includes several clinically important proteins such as P-glycoprotein (P-gp), multidrug resistance associated protein and the TAP transporters. The protein is comprised of two, six span membrane bound regions each connected to a nuclear binding factor which binds ATP.

Where is the CFTR located in the body?

Rev. 79, Suppl.: S23–S45, 1999. — The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of the ABC transporter family that forms a novel Cl − channel. It is located predominantly in the apical membrane of epithelia where it mediates transepithelial salt and liquid movement.

Where is the regulatory domain located in CFTR?

The Regulatory Domain. The R domain of CFTR is encoded by exon 13 and it spans the region between NBF1 and the second transmembrane region. It contains several potential sites for phosphorylation by cAMP-dependent PKA or PKC.

What is the function of the CFTR chloride channel?

Several observations suggested that CFTR might regulate epithelial Cl − channels, either through direct association or by pumping a Cl − channel regulatory factor into or out of epithelial cells. First, the primary structure of CFTR placed it in a family of transport proteins called ATP-binding cassette (ABC) transporters ( 2 65 ).