Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 22, Issue 10, Pages 795-802Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3087
Keywords
-
Funding
- Swiss National Science Foundation [PP00P3_128419, 200021_134521]
- National Center of Competence in Research ('NCCR Molecular Systems Engineering')
- European Research Council (FP7) [MOMP 281764]
- Swiss National Science Foundation (SNF) [200021_134521, PP00P3_128419] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
Chaperones increase the folding yields of soluble proteins by suppressing misfolding and aggregation, but how they modulate the folding of integral membrane proteins is not well understood. Here we use single-molecule force spectroscopy and NMR spectroscopy to observe the periplasmic holdase chaperones SurA and Skp shaping the folding trajectory of the large beta-barrel outer-membrane receptor FhuA from Escherichia coli. Either chaperone prevents FhuA from misfolding by stabilizing a dynamic, unfolded state, thus allowing the substrate to search for structural intermediates. During this search, the SurA-chaperoned FhuA polypeptide inserts beta-hairpins into the membrane in a stepwise manner until the beta-barrel is folded. The membrane acts as a free-energy sink for beta-hairpin insertion and physically separates transient folds from chaperones. This stabilization of dynamic unfolded states and the trapping of folding intermediates funnel the FhuA polypeptide toward the native conformation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available