Peptide binding consensus of the NHE‐RF‐PDZ1 domain matches the C‐terminal sequence of cystic fibrosis transmembrane conductance regulator (CFTR)

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Abstract
The Na+‐H+ exchanger regulatory factor (NHE‐RF) is a cytoplasmic phosphoprotein that was first found to be involved in protein kinase A mediated regulation of ion transport. NHE‐RF contains two distinct protein interaction PDZ domains: NHE‐RF‐PDZ1 and NHE‐RF‐PDZ2. However, their binding partners are currently unknown. Because PDZ domains usually bind to specific short linear C‐terminal sequences, we have carried out affinity selection of random peptides for specific sequences that interact with the NHE‐RF PDZ domains and found that NHE‐RF‐PDZ1 is capable of binding to the CFTR C‐terminus. The specific and tight association suggests a potential regulatory role of NHE‐RF in cystic fibrosis transmembrane conductance regulator (CFTR) function.