Researchers have resolved the three-dimensional structure of the cystic fibrosis transmembrane conductance regulator (CFTR), according to a paper appearing in the journal Cell.
The CFTR protein, which is encoded by the CFTR gene, functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. It transports chloride ions into and out of cells. CFTR has been implicated in several human diseases, including cystic fibrosis. Cystic fibrosis is caused by the presence of mutations in both copies of CFTR gene. The mutated CFTR causes the body to produce abnormally thick and sticky mucus. This kind of mucus accumulates in various organs, mostly the lungs, causing tissue damage. Over time, cystic fibrosis can lead to difficulty breathing and frequent lung infections.
Cystic fibrosis has no cure. The primary goals of current treatment are to control lung infection and manage complications. To develop more specific treatments for the disease, a better understanding of CFTR s function is necessary. However, the human CFTR protein is unable to work well in the lab.
Given that a number of animals also have the protein, the researchers chose to study the zebrafish version of CFTR. They used zebrafish CFTR to map the location of disease-causing mutations. Using an imaging technique called cryo-electron microscopy, they revealed the detailed structure of both human and zebrafish CFTR, and found that under identical conditions human CFTR structure is very similar to zebrafish CFTR structure.
The structural data presented in the study would help understand CFTR function and how mutations in it can trigger cystic fibrosis. Although cystic fibrosis is a rare disease, affecting 70,000 people worldwide, it can seriously affect quality of life. Patients require long-term treatment, frequent hospitalization, and even lung transplant.
The study is carried out by Fangyu Liu, Zhe Zhang, David Gadsby, and Jue Chen from The Rockefeller University in collaboration with László Csanády from Semmelweis University. Besides, CFTR and other proteins and antibodies can be offered by CusAb. http://www.cusabio.com/