8EIG

The complex of phosphorylated human delta F508 cystic fibrosis transmembrane conductance regulator (CFTR) with elexacaftor (VX-445) and ATP/Mg

8EIG の概要

• エントリーDOI: 10.2210/pdb8eig/pdb
• EMDBエントリー: 28155
• 分子名称: Cystic fibrosis transmembrane conductance regulator, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: abc transporter, ion channel, folding correction, membrane protein, atp-binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 170234.58

構造登録者

Fiedorczuk, K.,Chen, J. (登録日: 2022-09-15, 公開日: 2022-10-19, 最終更新日: 2025-05-14)

主引用文献

Fiedorczuk, K.,Chen, J.
Molecular structures reveal synergistic rescue of Delta 508 CFTR by Trikafta modulators.
Science, 378:284-290, 2022

PubMed Abstract: The predominant mutation causing cystic fibrosis, a deletion of phenylalanine 508 (Δ508) in the cystic fibrosis transmembrane conductance regulator (CFTR), leads to severe defects in CFTR biogenesis and function. The advanced therapy Trikafta combines the folding corrector tezacaftor (VX-661), the channel potentiator ivacaftor (VX-770), and the dual-function modulator elexacaftor (VX-445). However, it is unclear how elexacaftor exerts its effects, in part because the structure of Δ508 CFTR is unknown. Here, we present cryo-electron microscopy structures of Δ508 CFTR in the absence and presence of CFTR modulators. When used alone, elexacaftor partially rectified interdomain assembly defects in Δ508 CFTR, but when combined with a type I corrector, did so fully. These data illustrate how the different modulators in Trikafta synergistically rescue Δ508 CFTR structure and function.

PubMed: 36264792
DOI: 10.1126/science.ade2216

実験手法

ELECTRON MICROSCOPY (3.6 Å)