Folding of CFTR is predominantly cotranslational.
The folding process for newly synthesized, multispanning membrane proteins in the endoplasmic reticulum (ER) is largely unknown. Here, we describe early folding events of the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ABC-transporter family. In vitro translation of CFTR in the presence of semipermeabilized cells allowed us to investigate this protein during nascent chain elongation. We found that CFTR folds mostly during synthesis as determined by protease susceptibility. C-terminally truncated constructs showed that individual CFTR domains formed well-defined structures independent of C-terminal parts. We conclude that the multidomain protein CFTR folds mostly cotranslationally, domain by domain.
Kleizen
Bertrand
B
Cellular Protein Chemistry, Department of Chemistry, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
van Vlijmen
Thijs
T
de Jonge
Hugo R
HR
Braakman
Ineke
I
D045744:Cell Line, Tumor; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding
C505032:CFTR protein, human; D010446:Peptide Fragments; D019005:Cystic Fibrosis Transmembrane Conductance Regulator