Structural basis for misfolding at a disease phenotypic position in CFTR: Comparison of TM3/4 helix-loop-helix constructs with TM4 peptides

► A CF-phenotypic position in a helical hairpin is studied using all 20 amino acids. ► Residue hydrophobicity is the dominant effect on protein-detergent interactions. ► Mutant-mediated variations determine the extent of folding of a given construct. ► Our results may portend the structural consequences in a natural lipid bilayer.