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-Structure paper
Title | Molecular structure of the ATP-bound, phosphorylated human CFTR. |
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Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 115, Issue 50, Page 12757-12762, Year 2018 |
Publish date | Dec 11, 2018 |
Authors | Zhe Zhang / Fangyu Liu / Jue Chen / |
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 ...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. |
External links | Proc Natl Acad Sci U S A / PubMed:30459277 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.2 Å |
Structure data | |
Chemicals | ChemComp-MG: ChemComp-ATP: ChemComp-POV: ChemComp-CLR: |
Source |
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Keywords | HYDROLASE / ABC transporter / anion channel / cystic fibrosis / membrane protein |