EMD-9230

Single-particle
3.2 Å
EMD-9230 Deposition: 16/10/2018
Map released: 21/11/2018
Last modified: 13/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-9230

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

EMD-9230

Single-particle
3.2 Å
EMD-9230 Deposition: 16/10/2018
Map released: 21/11/2018
Last modified: 13/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: human cystic fibrosis transmembrane conductance regulator (CFTR)
Fitted models: 6msm (Avg. Q-score: 0.476)

Deposition Authors: Zhang Z, Liu F
Molecular structure of the ATP-bound, phosphorylated human CFTR.
Zhang Z, Liu F , Chen J
(2018) PNAS , 115 , 12757 - 12762
PUBMED: 30459277
DOI: doi:10.1073/pnas.1815287115
ISSN: 1091-6490
ASTM: PNASA6
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.