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Jussupow A, Messias AC, Stehle R, et al. The dynamics of linear polyubiquitin. Sci Adv. 2020;6(42)doi: 10.1126/sciadv.abc3786.
Jussupow, A., Messias, A. C., Stehle, R., Geerlof, A., Solbak, S. M. �. �., Paissoni, C., Bach, A., Sattler, M., & Camilloni, C. (2020). The dynamics of linear polyubiquitin. Science advances, 6(42), . https://doi.org/10.1126/sciadv.abc3786
Jussupow, Alexander, et al. "The dynamics of linear polyubiquitin." Science advances vol. 6,42 (2020). doi: https://doi.org/10.1126/sciadv.abc3786
Jussupow A, Messias AC, Stehle R, Geerlof A, Solbak SMØ, Paissoni C, Bach A, Sattler M, Camilloni C. The dynamics of linear polyubiquitin. Sci Adv. 2020 Oct 14;6(42). doi: 10.1126/sciadv.abc3786. Print 2020 Oct. PMID: 33055165; PMCID: PMC7556843.
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Sci Adv. 2020 Oct 14;6(42). doi: 10.1126/sciadv.abc3786. Print 2020 Oct.

The dynamics of linear polyubiquitin.

Science advances

Alexander Jussupow, Ana C Messias, Ralf Stehle, Arie Geerlof, Sara M Ø Solbak, Cristina Paissoni, Anders Bach, Michael Sattler, Carlo Camilloni

Affiliations

  1. Department of Chemistry and Institute for Advanced Study, Technical University of Munich, Garching 85747, Germany.
  2. Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
  3. Center for Integrated Protein Science Munich at Department of Chemistry, Technical University of Munich, Garching 85747, Germany.
  4. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
  5. Dipartimento di Bioscienze, Università degli studi di Milano, 20133 Milano, Italy.
  6. Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg 85764, Germany. [email protected] [email protected].
  7. Department of Chemistry and Institute for Advanced Study, Technical University of Munich, Garching 85747, Germany. [email protected] [email protected].

PMID: 33055165 PMCID: PMC7556843 DOI: 10.1126/sciadv.abc3786

Abstract

Polyubiquitin chains are flexible multidomain proteins, whose conformational dynamics enable them to regulate multiple biological pathways. Their dynamic is determined by the linkage between ubiquitins and by the number of ubiquitin units. Characterizing polyubiquitin behavior as a function of their length is hampered because of increasing system size and conformational variability. Here, we introduce a new approach to efficiently integrating small-angle x-ray scattering with simulations allowing us to accurately characterize the dynamics of linear di-, tri-, and tetraubiquitin in the free state as well as of diubiquitin in complex with NEMO, a central regulator in the NF-κB pathway. Our results show that the behavior of the diubiquitin subunits is independent of the presence of additional ubiquitin modules and that the dynamics of polyubiquitins with different lengths follow a simple model. Together with experimental data from multiple biophysical techniques, we then rationalize the 2:1 NEMO:polyubiquitin binding.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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