Unlocking the Structure of CFTR
Produced as part of a graduate molecular visualization course, this "Scientific American" two-page spread is designed to explain and visualize the structure of cystic fibrosis transmembrane conductance regular (CFTR). I used molecular structural data from primary databases to create a scientifically-accurate molecular visualizations of CFTR and its domains.
Audience: Educated lay audience
Client: Derek Ng BSc, MScBMC, PhD
Media:
Chimera
Adobe Photoshop CC
Adobe illustrator CC
Format: Print (magazine, 11x17 inches)
Date: May, 2017
Process Work
References
UniProtKB data: P13569 - CFTR human
PDB data: 5UAK - Dephosphorylated, ATP-free human CFTR
PDB data: 5UAR - Dephosphorylated, ATP-free zebrafish CFTR
PDB data: 2BBO - Human NBD1 with Phe508
PDB data: 4WZ6 - Human CFTR deltaF508 with three solubilizing mutations, bound ATP
PubChem CID: 16678941 - Lumacaftor
PubChem CID: 16220172 - Ivacaftor
Farinha, Carlos M, and Sara Canato. 2017. “From the Endoplasmic Reticulum to the Plasma Membrane : Mechanisms of CFTR Folding and Trafficking.” Cellular and Molecular Life Sciences 74 (1). Springer International Publishing: 39–55. doi:10.1007/s00018-016-2387-7.
Gadsby, David C, Paola Vergani, and László Csanády. 2006. “The ABC Protein Turned Chloride Channel Whose Failure Causes Cystic Fibrosis.” Nature 440 (23): 477–83. doi:10.1038/nature04712.
Hall, J. D., Wang, H., Byrnes, L. J., Shanker, S., Wang, K., Efremov, I. V., Chong, P. A., Forman-Kay, J. D. and Aulabaugh, A. E. 2016. “Binding screen for cystic fibrosis transmembrane conductance regulator correctors finds new chemical matter and yields insights into cystic fibrosis therapeutic strategy.” Protein Science, 25: 360–373. doi:10.1002/pro.2821
Kuk, Kelly, and Jennifer L Taylor-cousar. 2015. “Lumacaftor and Ivacaftor in the Management of Patients with Cystic Fibrosis : Current Evidence and Future Prospects.” Therapeutic Advances in Respiratory Disease 9 (6): 313–26. doi:10.1177/1753465815601934.
Lewis, H A, C Wang, X Zhao, Y Hamuro, K Conners, M C Kearins, F Lu, et al. 2010. “Structure and Dynamics of NBD1 from CFTR Characterized Using Crystallography and Hydrogen / Deuterium Exchange Mass Spectrometry.” Journal of Molecular Biology 396 (2). Elsevier Ltd: 406–30. doi:10.1016/j.jmb.2009.11.051.
Linsdell, P. Architecture and functional properties of the CFTR channel pore. Cellular and Molecular Life Sciences. 2017; 74: 67–83. doi: 10.1007/s00018-016-2389-5.
Lukacs, Gergely L., and A.S. Verkman. 2012. “CFTR: folding, misfolding and correcting the ΔF508 conformational defect.” Trends Mol Med. 18 (2): 81–91. doi:10.1016/j.molmed.2011.10.003.CFTR.
Meng, X., Clews, Kargas, V., Wang, and Ford, R. The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability. Cellular and Molecular Life Sciences. 2017; 74: 23–38. doi: 10.1007/s00018-016-2386-8
Thibodeau, P., Brautigam, C., Machius, M., and Thomas, P. Side chain and backbone contributions of Phe508 to CFTR folding. Nature Structural and Molecular Biology. 2005; 12: 10-16. doi: 10.1038/nsmb881.
Van Goor F et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proceedings of the National Academy of Sciences. 2009; 106: 18825–18830. doi: 10.1073/pnas.0904709106.
Vankeerberghen, A., Cuppens, H., and Cassiman, J. The cystic fibrosis transmembrane conductance regulator: An intriguing protein with pleiotropic functions. Journal of Cystic Fibrosis. 2002; 1: 13-29. doi: 10.1016/S1569-1993(01)00003-0.
Zhang Z and Chen, J. Atomic Structure of the Cystic Fibrosis Transmembrane Conductance Regulator. Cell. 2016; 167: 1586-1597. doi: 10.1016/j.cell.2016.11.014.