6MSM

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

6MSM の概要

• エントリーDOI: 10.2210/pdb6msm/pdb
• EMDBエントリー: 9230
• 分子名称: Cystic fibrosis transmembrane conductance regulator, Piece of Molecule-1, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: abc transporter, anion channel, cystic fibrosis, membrane protein, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 176067.40

構造登録者

Zhang, Z.,Liu, F.,Chen, J. (登録日: 2018-10-16, 公開日: 2018-11-21, 最終更新日: 2024-03-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.2 Å)