Introduction to Section IV: Biophysical Methods to Approach CFTR Structure
Inefficient folding of CFTR into a functional three-dimensional structure is the basic pathophysiologic mechanism leading to most cases of cystic fibrosis. Knowledge of the structure of CFTR and placement of these mutations into a structural context would provide information key for developing targeted therapeutic approaches for cystic fibrosis. As a large polytopic membrane protein containing disordered regions, intact CFTR has been refractory to efforts to solve a high-resolution structure using X-ray crystallography. The following chapters summarize current efforts to circumvent these obstacles by utilizing NMR, electron microscopy, and computational methodologies and by development of experimental models of the relevant domains of CFTR.
Key wordsCFTR structure NMR EM crystallography spectroscopy
The authors are grateful for the support provided by the NIH-NIDDK, Welch Foundation, and the CF Foundation for much of the work summarized. Also we would like to thank the many investigators that have contributed to these studies and our thinking regarding the utility of structural approaches including the authors of Chapters 22 , http://23 , and http://25 , the members of the CFTR folding consortium, the SGX-CFFT joint research committee, Chad Brautigam, Hanoch Senderowitz, Martin Mense, and former members of the laboratory at UT Southwestern, including Bao-He Qu, Elizabeth Strickland, Michael Dorwart, Patrick Thibodeau, John Richardson, Jarod Watson, and Emmanuel Caspa.
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