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Cystic fibrosis(CF),one of the most common inherited disease in the Caucasian population,is caused by mutations of the CF transmembrane conductance regulator(CFTR),a cAMP-regulated chloride channel localized at the apical plasma membrane(PM)of epithelia.CFTR comprises of two membrane spanning domains(MSD1,MSD2)and three cytosolic domains; a regulatory(R)and two nucleotide-binding domains(NBD1,NBD2).