6MSM

Phosphorylated, ATP-bound human cystic fibrosis transmembrane conductance regulator (CFTR)

Summary for 6MSM

• Entry DOI: 10.2210/pdb6msm/pdb
• EMDB information: 9230
• Descriptor: Cystic fibrosis transmembrane conductance regulator, Piece of Molecule-1, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: abc transporter, anion channel, cystic fibrosis, membrane protein, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 176067.40

Authors

Zhang, Z.,Liu, F.,Chen, J. (deposition date: 2018-10-16, release date: 2018-11-21, Last modification date: 2024-03-13)

Primary citation

Zhang, Z.,Liu, F.,Chen, J.
Molecular structure of the ATP-bound, phosphorylated human CFTR.
Proc. Natl. Acad. Sci. U.S.A., 115:12757-12762, 2018

PubMed Abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel important in maintaining proper functions of the lung, pancreas, and intestine. The activity of CFTR is regulated by ATP and protein kinase A-dependent phosphorylation. To understand the conformational changes elicited by phosphorylation and ATP binding, we present here the structure of phosphorylated, ATP-bound human CFTR, determined by cryoelectron microscopy to 3.2-Å resolution. This structure reveals the position of the R domain after phosphorylation. By comparing the structures of human CFTR and zebrafish CFTR determined under the same condition, we identified common features essential to channel gating. The differences in their structures indicate plasticity permitted in evolution to achieve the same function. Finally, the structure of CFTR provides a better understanding of why the G178R, R352Q, L927P, and G970R/D mutations would impede conformational changes of CFTR and lead to cystic fibrosis.

PubMed: 30459277
DOI: 10.1073/pnas.1815287115

Experimental method

ELECTRON MICROSCOPY (3.2 Å)