Combining Theoretical and Experimental Data to Decipher CFTR 3D Structures and Functions

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2018 May 21

PMID 29779042

Citations 12

Authors

Brice Hoffmann

Ahmad Elbahnsi

Pierre Lehn

Jean-Luc Decout

Fabio Pietrucci

Jean-Paul Mornon

Isabelle Callebaut

Affiliations

Soon will be listed here.

Abstract

Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to gain some insights into critical features of the conformational transition toward active CFTR forms. These critical elements lie within membrane-spanning domains but also within NBD1 and the N-terminal extension, in which conformational plasticity is predicted to occur to help the interaction with filamin, one of the CFTR cellular partners.

Citing Articles

ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.

Elbahnsi A, Dudas B, Callebaut I, Hinzpeter A, Miteva M Pharmaceuticals (Basel). 2025; 17(12.

PMID: 39770445 PMC: 11676857. DOI: 10.3390/ph17121602.

Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor.

Li H, Rodrat M, Al-Salmani M, Veselu D, Han S, Raraigh K J Physiol. 2024; 602(2):333-354.

PMID: 38186087 PMC: 10872379. DOI: 10.1113/JP285727.

Role of Hydrophobic Amino-Acid Side-Chains in the Narrow Selectivity Filter of the CFTR Chloride Channel Pore in Conductance and Selectivity.

Linsdell P J Membr Biol. 2023; 256(4-6):433-442.

PMID: 37823914 DOI: 10.1007/s00232-023-00294-w.

A Proteomic Survey of the Cystic Fibrosis Transmembrane Conductance Regulator Surfaceome.

Iazzi M, Sadeghi S, Gupta G Int J Mol Sci. 2023; 24(14).

PMID: 37511222 PMC: 10380767. DOI: 10.3390/ijms241411457.

Molecular dynamics study of Cl permeation through cystic fibrosis transmembrane conductance regulator (CFTR).

Zeng Z, Linsdell P, Pomes R Cell Mol Life Sci. 2023; 80(2):51.

PMID: 36694009 PMC: 9873711. DOI: 10.1007/s00018-022-04621-7.

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