CFTR protein

Cystic fibrosis (MIM 219700) Mutations in the gene encoding the CFTR protein, a Cl" transporter... 

Figure 41-17. Diagram of the structure of the CFTR protein (not to scale). The protein contains twelve transmembrane segments (probably helical), two nucleotide-binding folds or domains (NBFl and NBF2), and one regulatory (R) domain. NBFl and NBF2 probably bind ATP and couple its hydrolysis to transport of Cl . Phe 508, the major locus of mutations in cystic fibrosis, is located in NBFl.

Significant strides have been made in past decades with development of new therapies that have led to the ever-lengthening CF life-span. Since the discovery of the CF gene and the CFTR protein defect, research has focused on gene therapy as a way to restore normal CFTR function through DNA transfer. 

Approximately 90% of CF patients carry a loss-of-function CFTR mutation on at least one allele that results in deletion of phenylalanine 508 (F508del) in the first CFTR nucleotide-binding domain [7]. The F508del prevents the proper domain folding and assembly of the multidomain CFTR protein during its biogenesis in the endoplasmic... 

The majority of cases of cystic fibrosis result from deletion of phenylalanine at position 508 (AF508), which interferes with proper protein folding and the posttranslational processing of oligosaccharide side chains. The abnormal chloride channel protein (CFTR) is degraded by the cytosolic proteasome complex rather than being translocated to the cell membrane. Other functional defects in CFTR protein that teaches the cell membrane may also contribute to the pathogenesis of cystic fibrosis. 

Cystic fibrosis a hereditary disease in which there is a mutation in the CFTR protein. 

Cystic fibrosis is a life-threatening genetic disease caused by a dysfunctional cystic fibrosis transmembrane regulator, CFTR protein, which modulates salt and water transport into and out of cells. This ion-channel defect leads to poorly hydrated, thick, mucous secretions in the airways and severely impaired mucociliary func-... 

The ABC1 protein is a member of a large family of multidrug transporters, sometimes called ABC transporters because they all have ATP-binding cassettes they also have two transmembrane domains with six transmembrane helices (Chapter 11). These proteins actively transport a variety of ions, amino acids, vitamins, steroid hormones, and bile salts across plasma membranes. The CFTR protein that is defective in cystic fibrosis (see Box 11-3) is another member of this ABC family of multidrug transporters. 

In a patient with cystic fibrosis, the mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein folds incorrectly. The patient s cells modify this abnormal protein by attaching ubiquitin molecules to it. What is the fate of this modified CFTR protein ... 

An alternatively spliced isoform may form chloride channels in heart.1 - As mentioned in Chapter 8, Section C,5 the CFTR protein is a member of the... 

The CFTR protein can undergo endocytosis into clathrin-coated vesicles as part of its regulatory mechanism.0 Since HC03 is usually exchanged for Cl in epithelial ion transport, regulation of HC03 uptake is also a significant aspect of CFTR function ... 

The CFTR protein has additional medical significance. Its stimulation by bacterial toxins is respon-... 

CF is caused by a defect in the CFTR protein. This protein is a cAMP- and phosphorylation-regulated chloride ion channel, important in maintaining osmotic gradients and the movement of water across epithelial membranes. 

Egan ME, Glockner-Pagel J, Ambrose C, Cahill PA, Pappoe L, Balamuth N, Cho E, Canny S, Wagner CA, Geibel J, Caplan MJ. Calcium-pump inhibitors induce functional surface expression of Delta F508-CFTR protein in cystic fibrosis epithelial cells. Nat. Med. 2002 8 485-192. 

A.B., Aleksandrov, L.A., Riordan, J.R., and Ford, R.C. (2005) Crystallographic and single-particle analyses of native- and nucleotide-bound forms of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Biochemical Society Transactions, 33, 996-999. 

The CFTR protein consists of five domains two membrane spanning domains (MSDs), two nucleotidebinding domains (NBDs), and a regulatory domain (Figure 12-14). Both the amino terminus and carboxy terminus are located in the cytoplasm and each of the two membrane spanning domains contains six transmembrane... 

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