Molecular dynamics of the cryo-EM CFTR structure

H. Tordai, Ibolya Leveles, T. Hegedűs

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cystic fibrosis (CF), a lethal monogenic disease, is caused by mutant variants of the CF transmembrane conductance regulator (CFTR). Recent advances in single molecule cryo-EM methods enabled structural determination of full-length human and zebrafish CFTR, achieving an important milestone for CF drug development. To relate these structures to the gating cycle, we examined its dynamic features using molecular dynamics simulations. Our results show that the nucleotide binding domains (NBDs) in this bottom-open apo conformation exhibit motions related to dimerization and the bottom-closed apo CFTR model indicates opening of NBDs in contrast to transporters. These observations help in understanding the properties of CFTR chloride channel distinct from transporters and in proper interpretation of available structural information on this ABC protein.

Original languageEnglish
Pages (from-to)986-993
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume491
Issue number4
DOIs
Publication statusPublished - Sep 30 2017

Fingerprint

Molecular Dynamics Simulation
Cystic Fibrosis
Molecular dynamics
Nucleotides
Cystic Fibrosis Transmembrane Conductance Regulator
Chloride Channels
Dimerization
Zebrafish
Conformations
Molecules
Computer simulation
Pharmaceutical Preparations
Proteins

Keywords

  • CFTR
  • Computational biology
  • Cystic fibrosis
  • Molecular dynamics
  • Transmembrane protein structure

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Molecular dynamics of the cryo-EM CFTR structure. / Tordai, H.; Leveles, Ibolya; Hegedűs, T.

In: Biochemical and Biophysical Research Communications, Vol. 491, No. 4, 30.09.2017, p. 986-993.

Research output: Contribution to journalArticle

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