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The multiple phosphate-binding interactions to a common surface along NBD1 and the Lasso motif explain the well-known robustness to loss of any single phosphorylation site on the R-domain 9,11 and the requirement for an intact N-terminus containing the Lasso motif of CFTR for activity 33

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Key molecular features include the F23 Cagri residue anchoring the peptide at the receptor transmembrane (TM) bundle level and the micelle, an E14-R17 intramolecular salt bridge enhancing helical stability, and C-terminal P37 Cagri interaction with the receptor ECD

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