A combined analysis of the cystic fibrosis transmembrane conductance regulator: implications for structure and disease models

• Main Authors: Jian-min Chen, Chris Cutler, Caroline Jacques, Gilles Bœuf, Erick Denamur, Guillaume Lecointre, Bernard Mercier, Gordon Cramb
• Other Authors: The Pennsylvania State University CiteSeerX Archives
• Format: Text
• Language: English
• Published: 2001
• Subjects: Giganteus; Atlantic salmon; Salmo salar
• Online Access: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.532.2813; http://mbe.oxfordjournals.org/content/18/9/1771.full.pdf

Over the past decade, nearly 1,000 variants have been identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in classic and atypical cystic fibrosis (CF) patients worldwide, and an enormous wealth of information concerning the structure and function of the protein has also been accumulated. These data, if evaluated together in a sequence comparison of all currently available CFTR homologs, are likely to refine the global structure-function relationship of the protein, which will, in turn, facilitate interpretation of the identified mutations in the gene. Based on such a combined analysis, we had recently defined a ‘‘functional R domain’ ’ of the CFTR protein. First, presenting two full-length cDNA sequences (termed sCFTR-I and sCFTR-II) from the Atlantic salmon (Salmo salar) and an additional partial coding sequence from the eastern gray kangaroo (Macropus giganteus), this study went further to refine the boundaries of the two nucleotide-binding domains (NBDs) and the COOH-terminal tail (C-tail), wherein NBD1 was defined as going from P439 to G646, NBD2 as going from A1225 to E1417, and the C-tail as going from E1418 to L1480. This approach also provided further insights into the differential roles of the two halves of CFTR and highlighted several well-conserved motifs that may be involved in inter- or intramolecular