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Lambrughi M, Maiani E, Aykac Fas B, et al. Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs. Front Mol Biosci. 2021;8:676235doi: 10.3389/fmolb.2021.676235.
Lambrughi, M., Maiani, E., Aykac Fas, B., Shaw, G. S., Kragelund, B. B., Lindorff-Larsen, K., Teilum, K., Invernizzi, G., & Papaleo, E. (2021). Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs. Frontiers in molecular biosciences, 8676235. https://doi.org/10.3389/fmolb.2021.676235
Lambrughi, Matteo, et al. "Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs." Frontiers in molecular biosciences vol. 8 (2021): 676235. doi: https://doi.org/10.3389/fmolb.2021.676235
Lambrughi M, Maiani E, Aykac Fas B, Shaw GS, Kragelund BB, Lindorff-Larsen K, Teilum K, Invernizzi G, Papaleo E. Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs. Front Mol Biosci. 2021 Jun 28;8:676235. doi: 10.3389/fmolb.2021.676235. eCollection 2021. PMID: 34262938; PMCID: PMC8273247.
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Front Mol Biosci. 2021 Jun 28;8:676235. doi: 10.3389/fmolb.2021.676235. eCollection 2021.

Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs.

Frontiers in molecular biosciences

Matteo Lambrughi, Emiliano Maiani, Burcu Aykac Fas, Gary S Shaw, Birthe B Kragelund, Kresten Lindorff-Larsen, Kaare Teilum, Gaetano Invernizzi, Elena Papaleo

Affiliations

  1. Computational Biology Laboratory, Danish Cancer Society Research Center, Copenhagen, Denmark.
  2. Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milano, Italy.
  3. Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada.
  4. Structural Biology and NMR Laboratory and The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  5. Cancer Systems Biology, Section for Bioinformatics, Department of Health and Technology, Technical University of Denmark, Lyngby, Denmark.

PMID: 34262938 PMCID: PMC8273247 DOI: 10.3389/fmolb.2021.676235

Abstract

Ubiquitin is a small protein at the heart of many cellular processes, and several different protein domains are known to recognize and bind ubiquitin. A common motif for interaction with ubiquitin is the Ubiquitin Interacting Motif (UIM), characterized by a conserved sequence signature and often found in multi-domain proteins. Multi-domain proteins with intrinsically disordered regions mediate interactions with multiple partners, orchestrating diverse pathways. Short linear motifs for binding are often embedded in these disordered regions and play crucial roles in modulating protein function. In this work, we investigated the structural propensities of UIMs using molecular dynamics simulations and NMR chemical shifts. Despite the structural portrait depicted by X-crystallography of stable helical structures, we show that UIMs feature both helical and intrinsically disordered conformations. Our results shed light on a new class of disordered UIMs. This group is here exemplified by the C-terminal domain of one isoform of ataxin-3 and a group of ubiquitin-specific proteases. Intriguingly, UIMs not only bind ubiquitin. They can be a recruitment point for other interactors, such as parkin and the heat shock protein Hsc70-4. Disordered UIMs can provide versatility and new functions to the client proteins, opening new directions for research on their interactome.

Copyright © 2021 Lambrughi, Maiani, Aykac Fas, Shaw, Kragelund, Lindorff-Larsen, Teilum, Invernizzi and Papaleo.

Keywords: intrinsic disorder; molecular dynamics; moonlight functions; peptide arrays; short linear motifs; ubiquitin

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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