TY - JOUR
T1 - The cystic fibrosis transmembrane conductance regulator
T2 - Effects of the most common cystic fibrosis-causing mutation on the secondary structure and stability of a synthetic peptide
AU - Thomas, Philip J.
AU - Shenbagamurthi, Ponniah
AU - Sondek, John
AU - Hullihen, Joanne M.
AU - Pedersen, Peter L.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1992/3/25
Y1 - 1992/3/25
N2 - Deletion of phenylalanine 508 (ΔPhe-508) in the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes approximately 70% of all cases of cystic fibrosis. This residue lies in a region of the protein that we have synthesized chemically and shown to bind adenine nucleotides (Thomas, P. J., Shenbagamurthi, P., Ysern, X., and Pedersen, P. L. (1991) Science 251, 555-557). A peptide lacking this critical residue, but otherwise corresponding to this crucial part of the protein, now also has been chemically synthesized and purified. This mutant peptide (P-66) exhibits a significant loss of β-sheet structure as compared with the wild type peptide (P-67). Furthermore, urea denaturation of peptide structure reveals that P-66 is less stable than P-67. Although under non-denaturing conditions both peptides bind adenine nucleotides with high affinity, the loss of structural stability is reflected in the binding function of the peptides. Thus, P-67, in contrast to P-66, retains a significant capacity for nucleotide binding in 4 M urea. These results suggest a model for impaired ΔPhe-508 CFTR function.
AB - Deletion of phenylalanine 508 (ΔPhe-508) in the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes approximately 70% of all cases of cystic fibrosis. This residue lies in a region of the protein that we have synthesized chemically and shown to bind adenine nucleotides (Thomas, P. J., Shenbagamurthi, P., Ysern, X., and Pedersen, P. L. (1991) Science 251, 555-557). A peptide lacking this critical residue, but otherwise corresponding to this crucial part of the protein, now also has been chemically synthesized and purified. This mutant peptide (P-66) exhibits a significant loss of β-sheet structure as compared with the wild type peptide (P-67). Furthermore, urea denaturation of peptide structure reveals that P-66 is less stable than P-67. Although under non-denaturing conditions both peptides bind adenine nucleotides with high affinity, the loss of structural stability is reflected in the binding function of the peptides. Thus, P-67, in contrast to P-66, retains a significant capacity for nucleotide binding in 4 M urea. These results suggest a model for impaired ΔPhe-508 CFTR function.
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M3 - Article
C2 - 1372891
AN - SCOPUS:0026649584
SN - 0021-9258
VL - 267
SP - 5727
EP - 5730
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 9
ER -