How many transmembrane domains does CFTR?
CFTR’s domain organization largely corresponds to that of other ABC exporters, such as Sav1866 (14), MsbA (15), and TM(287/288) (16). Two transmembrane domains (TMD1 and TMD2), each comprising six transmembrane helices, form the pore for chloride ions and are connected by cytosolic loops (CL) and extracellular loops.
Is CFTR single spanning?
CFTR is organized into five putative domains, including two that are predicted to be transmembrane and consist of six membrane-spanning segments each.
What protein domains are present in the CFTR?
The CFTR is composed of five domains: two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory (R) domain.
How does CFTR get to the membrane?
If allowed to leave the ER, CFTR is modified at the Golgi and reaches the post-Golgi compartments to be delivered to the plasma membrane where it functions as a cAMP- and phosphorylation-regulated chloride/bicarbonate channel. CFTR residence at the membrane is a balance of membrane delivery, endocytosis, and recycling.
What does the CFTR gene do?
The CFTR protein The cystic fibrosis transmembrane conductance regulator (CFTR) protein is responsible for regulating the proper flow of chloride and sodium (a component of salt) in and out of the cell membranes in the lungs and other organs. is made up of 1,480 amino acids.
How many CFTR mutations are there?
More than 1,700 mutations of the CFTR gene have been identified. Although some are common, others are rare and found in only a few people.
What is the structure of CFTR?
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.
What kind of channel is CFTR?
The cystic fibrosis transmembrane conductance regulator ( CFTR The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a chloride channel that is responsible for regulating the proper flow of chloride and sodium (components of salt) in and out of the cell membranes in the lungs and other organs. )
How does the CFTR gene leads to the creation of the CFTR protein?
All proteins, including CFTR, are made of building blocks called amino acids. that are linked together into a long chain. The protein-building instructions spelled out in the CFTR gene. In people with CF, mutations in the CFTR gene cause the CFTR protein to malfunction, leading to a buildup of thick mucus.
Is CFTR a transmembrane conductance regulator?
Abstract 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.
Why is CFTR a ligand gated channel?
Second, CFTR is the only ligand-gated channel that consumes its ligand (ATP) during the gating cycle—a consequence of its enzymatic activity as an ABC transporter. We discuss these special properties of CFTR in the context of its evolutionary history as an ABC transporter.
Is cystic fibrosis transmembrane conductance regulator a nucleotide binding domain?
The first nucleotide binding domain of cystic fibrosis transmembrane conductance regulator is a site of stable nucleotide interaction, whereas the second is a site of rapid turnover. J Biol Chem277: 15419–15425 [PubMed] [Google Scholar]
Do β- and γ-phosphates work together to open CFTR channels?
These data emphasise the importance of the bond angle between the β- and γ-phosphates of ligands for the effective coupling of nucleotide binding to channel gating. Indeed, nucleotide triphosphates other than ATP effectively open the CFTR Cl−channel (Anderson et al.1991; Nagel et al.1992).