8 research outputs found
[Photograph 2012.201.B1306.0435]
Photograph used for a story in the Daily Oklahoman newspaper. Caption: "A tense moment from Oliver Halley's " Who's Happy Now?, " to be performed Wednesday.
Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell
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