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Dynamic aspects of pressure and temperature-stabilized intermediates of outer surface protein A
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  • Takuro Wakamoto,
  • Soichiro Kitazawa,
  • Tomoshi Kameda,
  • Ryo Kitahara
Takuro Wakamoto
Ritsumeikan Daigaku - Biwako Kusatsu Campus
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Soichiro Kitazawa
Ritsumeikan Daigaku - Biwako Kusatsu Campus
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Tomoshi Kameda
National Institute of Advanced Industrial Science and Technology Tokyo Bay Area Center
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Ryo Kitahara
Ritsumeikan University - Biwako Kusatsu Campus
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Abstract

Structural characterization of alternatively folded and partially disordered protein conformations remains challenging. Outer surface protein A (OspA) is a pivotal protein in Borrelia infection, which is the etiological agent of Lyme disease. OspA exists in equilibrium with intermediate conformations, in which the central and the C-terminal regions of the protein have lower stabilities than the N-terminal. Here, we characterize pressure- and temperature-stabilized intermediates of OspA by nuclear magnetic resonance spectroscopy combined with paramagnetic relaxation enhancement (PRE). We found that the C-terminal region of the intermediate was partially disordered; however, it retains weak specific contact with the N-terminal region, owing to a twist of the central β-sheet and increased flexibility in the polypeptide chain. The disordered C-terminal region of the pressure-stabilized intermediate was more compact than that of the temperature-stabilized form. Further, molecular dynamics simulation demonstrated that temperature-induced disordering of the β-sheet was initiated at the C-terminal region and continued through to the central region. An ensemble of simulation snapshots qualitatively described the PRE data from the intermediate and indicated that the intermediate structures of OspA may expose tick receptor-binding sites more readily than does the basic folded conformation.

Peer review status:ACCEPTED

06 Apr 2020Submitted to PROTEINS: Structure, Function, and Bioinformatics
06 Apr 2020Submission Checks Completed
06 Apr 2020Assigned to Editor
11 Apr 2020Reviewer(s) Assigned
29 Apr 2020Review(s) Completed, Editorial Evaluation Pending
29 Apr 2020Editorial Decision: Revise Minor
05 May 20201st Revision Received
06 May 2020Submission Checks Completed
06 May 2020Assigned to Editor
27 May 2020Reviewer(s) Assigned
05 Jun 2020Review(s) Completed, Editorial Evaluation Pending
06 Jun 2020Editorial Decision: Accept