2017年8月
Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell
NATURE COMMUNICATIONS
- 巻
- 8
- 号
- 1
- 開始ページ
- 398
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41467-017-00444-4
- 出版者・発行元
- NATURE PUBLISHING GROUP
Molecular chaperones are pivotal in folding and degradation of the cellular proteome but their impact on the conformational dynamics of near-native membrane proteins with disease relevance remains unknown. Here we report the effect of chaperone activity on the functional conformation of the temperature-sensitive mutant cystic fibrosis channel (Delta F508-CFTR) at the plasma membrane and after reconstitution into phospholipid bilayer. Thermally induced unfolding at 37 degrees C and concomitant functional inactivation of Delta F508-CFTR are partially suppressed by constitutive activity of Hsc70 and Hsp90 chaperone/co-chaperone at the plasma membrane and post-endoplasmic reticulum compartments in vivo, and at singlemolecule level in vitro, indicated by kinetic and thermodynamic remodeling of the mutant gating energetics toward its wild-type counterpart. Thus, molecular chaperones can contribute to functional maintenance of Delta F508-CFTR by reshaping the conformational energetics of its final fold, a mechanism with implication in the regulation of metastable ABC transporters and other plasma membrane proteins activity in health and diseases.
- リンク情報
- ID情報
-
- DOI : 10.1038/s41467-017-00444-4
- ISSN : 2041-1723
- PubMed ID : 28855508
- Web of Science ID : WOS:000408695100015