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Conformational landscapes of a class I ribonucleotide reductase complex during turnover reveal intrinsic dynamics and asymmetry

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  • Da Xu

    (Cornell University)

  • William C. Thomas

    (Cornell University
    Princeton University)

  • Audrey A. Burnim

    (Cornell University)

  • Nozomi Ando

    (Cornell University
    Princeton University)

Abstract

Understanding the structural dynamics associated with enzymatic catalysis has been a long-standing goal of biochemistry. With the advent of modern cryo-electron microscopy (cryo-EM), it has become conceivable to redefine a protein’s structure as the continuum of all conformations and their distributions. However, capturing and interpreting this information remains challenging. Here, we use classification and deep-learning-based analyses to characterize the conformational heterogeneity of a class I ribonucleotide reductase (RNR) during turnover. By converting the resulting information into physically interpretable 2D conformational landscapes, we demonstrate that RNR continuously samples a wide range of motions while maintaining surprising asymmetry to regulate the two halves of its turnover cycle. Remarkably, we directly observe the appearance of highly transient conformations needed for catalysis, as well as the interaction of RNR with its endogenous reductant thioredoxin also contributing to the asymmetry and dynamics of the enzyme complex. Overall, this work highlights the role of conformational dynamics in regulating key steps in enzyme mechanisms.

Suggested Citation

  • Da Xu & William C. Thomas & Audrey A. Burnim & Nozomi Ando, 2025. "Conformational landscapes of a class I ribonucleotide reductase complex during turnover reveal intrinsic dynamics and asymmetry," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57735-4
    DOI: 10.1038/s41467-025-57735-4
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    References listed on IDEAS

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    1. Brian D. Cook & Sarah M. Narehood & Kelly L. McGuire & Yizhou Li & F. Akif Tezcan & Mark A. Herzik, 2025. "Preparation of oxygen-sensitive proteins for high-resolution cryoEM structure determination using blot-free vitrification," Nature Communications, Nature, vol. 16(1), pages 1-11, December.

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