Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI117311

Cystic fibrosis transmembrane conductance regulator mutations that disrupt nucleotide binding.

J Logan, D Hiestand, P Daram, Z Huang, D D Muccio, J Hartman, B Haley, W J Cook, and E J Sorscher

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Logan, J. in: PubMed | Google Scholar

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Hiestand, D. in: PubMed | Google Scholar

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Daram, P. in: PubMed | Google Scholar

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Huang, Z. in: PubMed | Google Scholar

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Muccio, D. in: PubMed | Google Scholar

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Hartman, J. in: PubMed | Google Scholar

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Haley, B. in: PubMed | Google Scholar

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Cook, W. in: PubMed | Google Scholar

Department of Biochemistry University of Kentucky Lexington 40536.

Find articles by Sorscher, E. in: PubMed | Google Scholar

Published July 1, 1994 - More info

Published in Volume 94, Issue 1 on July 1, 1994
J Clin Invest. 1994;94(1):228–236. https://doi.org/10.1172/JCI117311.
© 1994 The American Society for Clinical Investigation
Published July 1, 1994 - Version history
View PDF
Abstract

Increasing evidence suggests heterogeneity in the molecular pathogenesis of cystic fibrosis (CF). Mutations such as deletion of phenylalanine at position 508 (delta F508) within the cystic fibrosis transmembrane conductance regulator (CFTR), for example, appear to cause disease by abrogating normal biosynthetic processing, a mechanism which results in retention and degradation of the mutant protein within the endoplasmic reticulum. Other mutations, such as the relatively common glycine-->aspartic acid replacement at CFTR position 551 (G551D) appear to be normally processed, and therefore must cause disease through some other mechanism. Because delta F508 and G551D both occur within a predicted nucleotide binding domain (NBD) of the CFTR, we tested the influence of these mutations on nucleotide binding by the protein. We found that G551D and the corresponding mutation in the CFTR second nucleotide binding domain, G1349D, led to decreased nucleotide binding by CFTR NBDs, while the delta F508 mutation did not alter nucleotide binding. These results implicate defective ATP binding as contributing to the pathogenic mechanism of a relatively common mutation leading to CF, and suggest that structural integrity of a highly conserved region present in over 30 prokaryotic and eukaryotic nucleotide binding domains may be critical for normal nucleotide binding.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 228
page 228
icon of scanned page 229
page 229
icon of scanned page 230
page 230
icon of scanned page 231
page 231
icon of scanned page 232
page 232
icon of scanned page 233
page 233
icon of scanned page 234
page 234
icon of scanned page 235
page 235
icon of scanned page 236
page 236
Version history
  • Version 1 (July 1, 1994): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts