Preprints
https://doi.org/10.5194/mr-2021-35
https://doi.org/10.5194/mr-2021-35

  08 Apr 2021

08 Apr 2021

Review status: this preprint is currently under review for the journal MR.

Detecting segmental anisotropic diffusion in disordered proteins by cross-correlated spin-relaxation

Clemens Kauffmann1,, Irene Ceccolini1,, Georg Kontaxis1, and Robert Konrat1 Clemens Kauffmann et al.
  • 1Department of Structural and Computational Biology, Max Perutz Laboratories, University of Vienna, Vienna Biocenter Campus 5, A-1030 Vienna, Austria
  • These authors contributed equally to this work.

Abstract. Among the numerous contributions of Geoffrey Bodenhausen to NMR spectroscopy his developments in the field of spin-relaxation methodology and theory will definitely have a long lasting impact. Starting with his seminal contributions to the excitation of multiple-quantum coherences he and his group thoroughly investigated the intricate relaxation properties of these “forbidden fruits” and developed experimental techniques to reveal the relevance of previously largely ignored cross-correlated relaxation (CCR) effects, as “the essential is invisible to the eyes”. Here we want to discuss CCR within the challenging context of intrinsically disordered proteins (IDPs) and emphasize its potential and relevance for the studies of structural dynamics of IDPs in the future years to come. Conventionally, dynamics of globularly folded proteins are modeled and understood as deviations from otherwise rigid structures tumbling in solution. However, with increasing protein flexibility, as observed for IDPs, this apparent dichotomy between structure and dynamics becomes blurred. Although complex dynamics and ensemble averaging might impair the extraction of mechanistic details even further, spin-relaxation uniquely encodes a protein’s structural memory, i.e. the temporal persistence of concerted motions and structural arrangements. Due to significant methodological developments, such as high-dimensional non-uniform sampling techniques, spin-relaxation in IDPs can now be monitored in unprecedented resolution. Not embedded within a rigid globular fold, conventional 15N spin probes might not suffice to capture the inherently local nature of IDP dynamics. To better describe and understand possible segmental motions of IDPs, we propose an experimental approach to detect the signature of diffusion anisotropy by quantifying cross-correlated spin relaxation of individual 15N1HN and 13C'13Cα spin pairs. By adapting Geoffrey Bodenhausen’s symmetrical reconversion principle to obtain zero frequency spectral density values we can define and demonstrate more sensitive means to characterize segmental anisotropic diffusion in IDPs.

Clemens Kauffmann et al.

Status: open (until 08 May 2021)

Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse
  • RC1: 'Comment on mr-2021-35', Anonymous Referee #1, 17 Apr 2021 reply
  • RC2: 'Please see attached file.', Anonymous Referee #2, 22 Apr 2021 reply
  • RC3: 'Comment on mr-2021-35', Anonymous Referee #2, 01 May 2021 reply
    • AC3: 'Reply on RC3', Clemens Kauffmann, 05 May 2021 reply
      • AC4: 'Reply on AC3', Clemens Kauffmann, 06 May 2021 reply

Clemens Kauffmann et al.

Clemens Kauffmann et al.

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Short summary
Unlike rigid folded proteins, intrinsically disordered proteins (IDPs) exist as an ensemble of dynamically interconverting structures. Cross-correlated spin-relaxation experiments are particularly suited to characterize the structural dynamics of IDPs as they encode a protein's "structural memory". By translating diffusion models of folded proteins to segmental motions in IDPs, we define an unambiguous experimental measure for the presence of anisotropic dynamics in the protein backbone.