Chaperones Skp and SurA dynamically expand unfolded OmpX and synergistically disassemble oligomeric aggregates.
Proc Natl Acad Sci U S A
Proceedings of the National Academy of Sciences
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Chamachi, N., Hartmann, A., Ma, M. Q., Svirina, A., Krainer, G., & Schlierf, M. (2022). Chaperones Skp and SurA dynamically expand unfolded OmpX and synergistically disassemble oligomeric aggregates.. Proc Natl Acad Sci U S A, 119 (9) https://doi.org/10.1073/pnas.2118919119
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.
Protein folding, Disaggregation, Chaperones, Single-molecule Fret, Outer Membrane Protein Biogenesis, Biopolymers, Bacterial Outer Membrane Proteins, Molecular Chaperones, Fluorescence Resonance Energy Transfer, Protein Conformation
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (841466)
External DOI: https://doi.org/10.1073/pnas.2118919119
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335498
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/