5UAK

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

Replaces:  5U71

Summary for 5UAK

• Entry DOI: 10.2210/pdb5uak/pdb
• Related: 5UAR
• EMDB information: 8461 8516
• Descriptor: Cystic fibrosis transmembrane conductance regulator (2 entities in total)
• Functional Keywords: abc transporter, anion channel, cystic fibrosis, membrane protein, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Early endosome membrane ; Multi-pass membrane protein : P13569
• Total number of polymer chains: 2
• Total formula weight: 170988.58

Authors

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

Primary citation

Liu, F.,Zhang, Z.,Csanady, L.,Gadsby, D.C.,Chen, J.
Molecular Structure of the Human CFTR Ion Channel.
Cell, 169:85-95.e8, 2017

PubMed Abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of dephosphorylated human CFTR without nucleotides, determined by electron cryomicroscopy (cryo-EM). Close resemblance of this human CFTR structure to zebrafish CFTR under identical conditions reinforces its relevance for understanding CFTR function. The human CFTR structure reveals a previously unresolved helix belonging to the R domain docked inside the intracellular vestibule, precluding channel opening. By analyzing the sigmoid time course of CFTR current activation, we propose that PKA phosphorylation of the R domain is enabled by its infrequent spontaneous disengagement, which also explains residual ATPase and gating activity of dephosphorylated CFTR. From comparison with MRP1, a feature distinguishing CFTR from all other ABC transporters is the helix-loop transition in transmembrane helix 8, which likely forms the structural basis for CFTR's channel function.

PubMed: 28340353
DOI: 10.1016/j.cell.2017.02.024

Experimental method

ELECTRON MICROSCOPY (3.87 Å)