PUBLICATION
Molecular structure of the ATP-bound, phosphorylated human CFTR
- Authors
- Zhang, Z., Liu, F., Chen, J.
- ID
- ZDB-PUB-181127-29
- Date
- 2018
- Source
- Proceedings of the National Academy of Sciences of the United States of America 115(50): 12757-12762 (Journal)
- Registered Authors
- Keywords
- ABC transporter, anion channel, cryo-EM, human CFTR
- MeSH Terms
-
- Adenosine Triphosphate/chemistry*
- Adenosine Triphosphate/metabolism*
- Animals
- Cell Line
- Cryoelectron Microscopy/methods
- Cyclic AMP-Dependent Protein Kinases/chemistry
- Cyclic AMP-Dependent Protein Kinases/metabolism
- Cystic Fibrosis/metabolism
- Cystic Fibrosis Transmembrane Conductance Regulator/chemistry*
- Cystic Fibrosis Transmembrane Conductance Regulator/metabolism*
- HEK293 Cells
- Humans
- Ion Channel Gating/physiology
- Ion Transport/physiology
- Molecular Structure
- Mutation/genetics
- Phosphorylation
- Zebrafish
- PubMed
- 30459277 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Zhang, Z., Liu, F., Chen, J. (2018) Molecular structure of the ATP-bound, phosphorylated human CFTR. Proceedings of the National Academy of Sciences of the United States of America. 115(50):12757-12762.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping