Two Salt Bridges Differentially Contribute to the Maintenance of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channel Function

• Type of Material: Article
• Authors: Guiying Cui, Emory University; Cody S. Freeman, Emory University; Taylor Knotts, Emory University; Chengyu Z. Prince, Emory University; Christopher Kuang, Emory University; Nael McCarty, Emory University
• Language: English
• Date: 2013-07-12
• Publisher: American Society for Biochemistry and Molecular Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
• Final Published Version (URL): http://www.jbc.org/content/288/28/20758
• Title of Journal or Parent Work: Journal of Biological Chemistry
• ISSN: 0021-9258
• Volume: 288
• Issue: 28
• Start Page: 20758
• End Page: 20767
• Grant/Funding Information: This work was supported, in whole or in part, by National Institutes of Health Grant R01-DK056481 (to N. M.).
• Keywords: Salt Bridge; ABC Transporter; Oocyte; Pore; MTS Reagents; Gating; CFTR; Xenopus
• Research Categories: Health Sciences, Immunology

Abstract

Background: Two salt bridges, Arg347–Asp924 and Arg352–Asp993, have been identified in CFTR, but the timing of their interaction remains unknown. Results: Arg347-Asp924-Asp993 form a triangular salt bridge and work together with the Arg352-Asp993 salt bridge to maintain the open pore architecture of CFTR. Conclusion: These salt bridge residues interact and contribute differently in stabilizing the open pore during gating cycle. Significance: Understanding the CFTR pore dynamic open-closed transition is crucial for rational drug design.