Cystic fibrosis transmembrane conductance regulator: Nucleotide binding to a synthetic peptide

Philip J. Thomas, P. Shenbagamurthi, Xavier Ysern, Peter L. Pedersen

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Multiple mutations in the gene responsible for cystic fibrosis are located within a region predicted to encode a nucleotide-binding fold in the amino terminal half of the cystic fibrosis transmembrane conductance regulator protein. A 67-amino acid peptide (P-67) that corresponds to the central region of this putative nucleotide binding site was chemically synthesized and purified. This peptide bound adenine nucleotides. The apparent dissociation constants (Kd's) for the trinitrophenyl (TNP) adenine nucleotides, TNP-adenosine triphosphate, TNP-adenosine diphosphate, and TNP-adenosine monophosphate, were 300 nanomolar, 200 nanomolar, and greater than 1 micromolar, respectively. The Kd for adenosine triphosphate was 300 micromolar. Circular dichroism spectroscopy was used to show that P-67 assumes a predominantly β sheet structure in solution, a finding that is consistent with secondary structure predictions. On the basis of this information, the phenylalanine at position 508, which is deleted in approximately 70 percent of individuals with cystic fibrosis, was localized to a β strand within the nucleotide binding peptide. Deletion of this residue is predicted to induce a significant structural change in the β strand and altered nucleotide binding.

Original languageEnglish (US)
Pages (from-to)555-557
Number of pages3
Issue number4993
StatePublished - Feb 1 1991

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Cystic fibrosis transmembrane conductance regulator: Nucleotide binding to a synthetic peptide'. Together they form a unique fingerprint.

Cite this