CFTR Protein Domains

Knowledge of cystic fibrosis transmembrane conductance regulator (CFTR) protein structure will contribute toward the understanding of CFTR function and CF biology, the mechanisms of action for CF drugs, and provide additional insight toward new drug discovery through structure-based drug design.

CFTR Protein Production Core at the University of Alabama at Birmingham

The CFTR Protein Distribution Program offers high-quality full-length recombinant cystic fibrosis transmembrane conductance regulator (CFTR) proteins expressed in and purified from mammalian cells. Wild-type, stabilized, and CF-causing CFTR variants are available.

CFTR Proteins

The CFTR Protein Production Core is supported and administered by the Cystic Fibrosis Foundation and capitalizes on the CFTR protein expression and purification expertise at Dr. John Kappes' laboratory with Dr. Zhengrong Yang at the University of Alabama at Birmingham (UAB).

Up to milligram quantities of analytically pure, properly folded, and biochemically active protein can be provided. For example, 3D structures have been determined by cryoEM [1], all exhibit a clear thermal unfolding transition,2,3 high ATPase activity (except for those containing ATPase incompetent mutations)2,3 and channel function.2-4 These proteins are suitable for biochemical, biophysical and structural studies. 

View a table detailing available protein constructs. Other constructs will be available upon request. Cells or cell membranes are also available if preferred.

Overview of the Ordering Process

  1. Please contact John Kappes at johnkappes@uabmc.edu and Zhengrong (Wendy) Yang at yangzw@uab.edu to discuss your specific needs and/or questions.
  2. After discussion and determination that the Core can meet your needs, the requestor should download the MTA out form and follow instructions for completion of an MTA between the supplying institution, UAB, and the requesting institution.
  3. Once an MTA is received, the requestor will be sent a CFTR Protein Production Order Form to complete.
  4. Upon receipt of the Order Form, the requestor will be contacted by either Dr. Kappes or Dr. Yang to finalize the request and will be provided with an estimated delivery date.
  5. A nominal fee will be charged for each batch of protein, membranes or cells, which may be paid through a purchase order.

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References

  1. “The allosteric effects of the F508del mutation in human CFTR elucidated by cryo-EM enabled by protein engineering,” presented by John F. Hunt, Columbia University, at the 16th ECFS Basic Science Conference Pre-Conference Meeting entitled “CFTR: new insights on structure and function and implications for modulation,” in Dubrovnik, Croatia, 27 March 2019. Manuscript in preparation.
  2. Yang, Z., et al., Structural stability of purified human CFTR is systematically improved by mutations in nucleotide binding domain 1. Biochim Biophys Acta, 2018. 1860(5): p. 1193-1204.
  3. Hildebrandt, E., et al., Specific stabilization of CFTR by phosphatidylserine. Biochim Biophys Acta, 2017. 1859(2): p. 289-293.
  4. Hildebrandt, E., et al., A stable human-cell system overexpressing cystic fibrosis transmembrane conductance regulator recombinant protein at the cell surface. Mol Biotechnol, 2015. 57(5): p. 391-405.

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