A 2-DOMAIN MODEL FOR THE R-DOMAIN OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR BASED ON SEQUENCE SIMILARITIES

CFTR belongs to a group of proteins sharing the structural motif of six transmembrane helices and a nucleotide binding domain. Unique to CFTR is the R domain, a charged cytoplasmic domain. Comparison of R domain sequences from ten species revealed that the N-terminal third is highly conserved, while the C-terminal two-thirds is poorly conserved. The R domain shows no strong sequence similarity to known proteins; however, 14 viral pol proteins show limited similarity to fragments of the R domain. Analysis revealed a relationship between the N- and C-terminal fragments of the R domain and two discontinuous fragments of the pol protein. These observations support a two-domain model for the R domain.