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TitleAtomic Structure of the Cystic Fibrosis Transmembrane Conductance Regulator.
Journal, issue, pagesCell, Vol. 167, Issue 6, Page 1586-11597.e9, Year 2016
Publish dateDec 1, 2016
AuthorsZhe Zhang / Jue Chen /
PubMed AbstractThe cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from the ATP-binding cassette (ABC) transporter family. In this study, we determined the structure of ...The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from the ATP-binding cassette (ABC) transporter family. In this study, we determined the structure of zebrafish CFTR in the absence of ATP by electron cryo-microscopy to 3.7 Å resolution. Human and zebrafish CFTR share 55% sequence identity, and 42 of the 46 cystic-fibrosis-causing missense mutational sites are identical. In CFTR, we observe a large anion conduction pathway lined by numerous positively charged residues. A single gate near the extracellular surface closes the channel. The regulatory domain, dephosphorylated, is located in the intracellular opening between the two nucleotide-binding domains (NBDs), preventing NBD dimerization and channel opening. The structure also reveals why many cystic-fibrosis-causing mutations would lead to defects either in folding, ion conduction, or gating and suggests new avenues for therapeutic intervention.
External linksCell / PubMed:27912062
MethodsEM (single particle)
Resolution3.73 - 3.87 Å
Structure data

8461

5uar

EMDB-8461: Structure of the cystic fibrosis transmembrane conductance regulator (CFTR) from zebrafish
PDB-5uar: Dephosphorylated, ATP-free cystic fibrosis transmembrane conductance regulator (CFTR) from zebrafish
Method: EM (single particle) / Resolution: 3.73 Å

EMDB-8516:
Structure of human cystic fibrosis transmembrane conductance regulator (CFTR)
Method: EM (single particle) / Resolution: 3.87 Å

Chemicals

ChemComp-D10:
DECANE

Source
  • danio rerio (zebrafish)
  • Homo sapiens (human)
KeywordsMEMBRANE PROTEIN / HYDROLASE / ABC transporter / anion channel / cystic fibrosis

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