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

Neharika Chamachi, Andreas Hartmann, Mai Quynh Ma, Anna Svirina, Georg Krainer, Michael Schlierf

Proceedings of the National Academy of Sciences of the United States of America 2022 Mar 01

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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. Copyright © 2022 the Author(s). Published by PNAS.

Citation

Neharika Chamachi, Andreas Hartmann, Mai Quynh Ma, Anna Svirina, Georg Krainer, Michael Schlierf. Chaperones Skp and SurA dynamically expand unfolded OmpX and synergistically disassemble oligomeric aggregates. Proceedings of the National Academy of Sciences of the United States of America. 2022 Mar 01;119(9)