Chaperones Skp and SurA dynamically expand unfolded OmpX and synergistically disassemble oligomeric aggregates

Research output: Contribution to journalResearch articleContributedpeer-review


Periplasmic chaperones 17-kilodalton protein (Skp) and survival factor A (SurA) are essential players in outer membrane protein (OMP) biogenesis. They prevent unfolded OMPs from misfolding during their passage through the periplasmic space and aid in the disassembly of OMP aggregates under cellular stress conditions. However, functionally important links between interaction mechanisms, structural dynamics, and energetics that underpin both Skp and SurA associations with OMPs have remained largely unresolved. Here, using single-molecule fluorescence spectroscopy, we dissect the conformational dynamics and thermodynamics of Skp and SurA binding to unfolded OmpX and explore their disaggregase activities. We show that both chaperones expand unfolded OmpX distinctly and induce microsecond chain reconfigurations in the client OMP structure. We further reveal that Skp and SurA bind their substrate in a fine-tuned thermodynamic process via enthalpy–entropy compensation. Finally, we observed synergistic activity of both chaperones in the disaggregation of oligomeric OmpX aggregates. Our findings provide an intimate view into the multifaceted functionalities of Skp and SurA and the fine-tuned balance between conformational flexibility and underlying energetics in aiding chaperone action during OMP biogenesis.


Original languageEnglish
Article numbere2118919119
JournalProceedings of the National Academy of Sciences of the United States of America : PNAS
Issue number9
Publication statusPublished - 25 Feb 2022

External IDs

PubMed 35217619
unpaywall 10.1073/pnas.2118919119
WOS 000766704900008
Mendeley a0174ba8-4e75-3b96-b227-5e58519d3e77
ORCID /0000-0002-6209-2364/work/142237665
ORCID /0000-0002-2213-2763/work/142239772
ORCID /0000-0002-4657-9092/work/142247775



  • Bacterial Outer Membrane Proteins/chemistry, Biopolymers/metabolism, Fluorescence Resonance Energy Transfer/methods, Molecular Chaperones/chemistry, Protein Conformation, disaggregation, single-molecule FRET, protein folding, chaperones, outer membrane protein biogenesis

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