Allosteric modulation balances thermodynamic stability and restores function of ΔF508 CFTR.

@article{Aleksandrov2012AllostericMB,
  title={Allosteric modulation balances thermodynamic stability and restores function of ΔF508 CFTR.},
  author={A. Aleksandrov and Pradeep Kota and L. Cui and Tim Jensen and A. Alekseev and Santiago Reyes and L. He and M. Gentzsch and L. Aleksandrov and N. Dokholyan and J. Riordan},
  journal={Journal of molecular biology},
  year={2012},
  volume={419 1-2},
  pages={
          41-60
        }
}
  • A. Aleksandrov, Pradeep Kota, +8 authors J. Riordan
  • Published 2012
  • Biology, Medicine
  • Journal of molecular biology
    • Most cystic fibrosis is caused by a deletion of a single residue (F508) in CFTR (cystic fibrosis transmembrane conductance regulator) that disrupts the folding and biosynthetic maturation of the ion channel protein. Progress towards understanding the underlying mechanisms and overcoming the defect remains incomplete. Here, we show that the thermal instability of human ΔF508 CFTR channel activity evident in both cell-attached membrane patches and planar phospholipid bilayers is not observed in… CONTINUE READING
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    References

    Publications referenced by this paper.
    SHOWING 1-10 OF 74 REFERENCES
    CFTR: folding, misfolding and correcting the ΔF508 conformational defect.
    • 262
    Regulatory insertion removal restores maturation, stability and function of DeltaF508 CFTR.
    • 95
    • PDF
    Limited proteolysis as a probe for arrested conformational maturation of ΔF508 CFTR
    • 106
    Localization and Suppression of a Kinetic Defect in Cystic Fibrosis Transmembrane Conductance Regulator Folding*
    • 142
    • PDF
    The ΔF508 cystic fibrosis mutation impairs domain-domain interactions and arrests post-translational folding of CFTR
    • 302
    Domain interdependence in the biosynthetic assembly of CFTR.
    • 188
    Phenylalanine-508 mediates a cytoplasmic–membrane domain contact in the CFTR 3D structure crucial to assembly and channel function
    • 361
    • PDF
    Integrated biophysical studies implicate partial unfolding of NBD1 of CFTR in the molecular pathogenesis of F508del cystic fibrosis
    • 81
    Impact of the ΔF508 Mutation in First Nucleotide-binding Domain of Human Cystic Fibrosis Transmembrane Conductance Regulator on Domain Folding and Structure*
    • 269
    • PDF
    Thermally Unstable Gating of the Most Common Cystic Fibrosis Mutant Channel (ΔF508)
    • 43
    • Highly Influential
    • PDF