5UAR

Dephosphorylated, ATP-free cystic fibrosis transmembrane conductance regulator (CFTR) from zebrafish

Replaces:  5TSI

Summary for 5UAR

• Entry DOI: 10.2210/pdb5uar/pdb
• Related: 5UAK
• EMDB information: 8461 8516
• Descriptor: Cystic fibrosis transmembrane conductance regulator, DECANE (2 entities in total)
• Functional Keywords: abc transporter, anion channel, cystic fibrosis, membrane protein, hydrolase
• Biological source: Danio rerio (Zebrafish)
• Total number of polymer chains: 1
• Total formula weight: 169906.36

Authors

Zhang, Z.,Chen, J. (deposition date: 2016-12-19, release date: 2017-01-18, Last modification date: 2024-03-06)

Primary citation

Zhang, Z.,Chen, J.
Atomic Structure of the Cystic Fibrosis Transmembrane Conductance Regulator.
Cell, 167:1586-1597.e9, 2016

PubMed Abstract: 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.

PubMed: 27912062
DOI: 10.1016/j.cell.2016.11.014

Experimental method

ELECTRON MICROSCOPY (3.73 Å)