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Lighting up Nobel Prize-winning studies with protein intrinsic disorder

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Abstract

Intrinsically disordered proteins and regions (IDPs and IDRs) and their importance in biology are becoming increasingly recognized in biology, biochemistry, molecular biology and chemistry textbooks, as well as in current protein science and structural biology curricula. We argue that the sequence → dynamic conformational ensemble → function principle is of equal importance as the classical sequence → structure → function paradigm. To highlight this point, we describe the IDPs and/or IDRs behind the discoveries associated with 17 Nobel Prizes, 11 in Physiology or Medicine and 6 in Chemistry. The Nobel Laureates themselves did not always mention that the proteins underlying the phenomena investigated in their award-winning studies are in fact IDPs or contain IDRs. In several cases, IDP- or IDR-based molecular functions have been elucidated, while in other instances, it is recognized that the respective protein(s) contain IDRs, but the specific IDR-based molecular functions have yet to be determined. To highlight the importance of IDPs and IDRs as general principle in biology, we present here illustrative examples of IDPs/IDRs in Nobel Prize-winning mechanisms and processes.

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Funding

All authors acknowledge financial support by the DFG (RTG 2467, project number 391498659 ‘Intrinsically Disordered Proteins—Molecular Principles, Cellular Functions, and Diseases’).

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Authors and Affiliations

  1. Research Training Group RTG2467, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany

    Lolita Piersimoni, Marina Abd el Malek, Twinkle Bhatia, Julian Bender, Christin Brankatschk, Jaime Calvo Sánchez, Alessio Di Ianni, Jhonny Oscar Figueroa Parra, Dailen Garcia-Martinez, Julia Hesselbarth, Janett Köppen, Luca M. Lauth, Laurin Lippik, Lisa Machner, Shubhra Sachan, Lisa Schmidt, Robin Selle, Ioannis Skalidis, Oleksandr Sorokin, Daniele Ubbiali, Bruno Voigt, Alice Wedler, Alan An Jung Wei, Peter Zorn, Marcel Köhn & Andrea Sinz

  2. Department of Chemistry, College of Art and Sciences, University of South Florida, Tampa, FL, 33620, USA

    Guy W. Dayhoff

  3. Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Alan Keith Dunker

  4. Department of Molecular Medicine, USF Health Byrd Alzheimer’s Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Vladimir N. Uversky

Authors
  1. Lolita Piersimoni
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  2. Marina Abd el Malek
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  14. Laurin Lippik
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  15. Lisa Machner
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  16. Shubhra Sachan
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  17. Lisa Schmidt
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  18. Robin Selle
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  22. Bruno Voigt
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  23. Alice Wedler
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  24. Alan An Jung Wei
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  25. Peter Zorn
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  26. Alan Keith Dunker
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  27. Marcel Köhn
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  28. Andrea Sinz
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  29. Vladimir N. Uversky
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Contributions

AKD conceived the idea. LP, MK, AS, and VNU wrote and assembled the manuscript. LP and VNU designed figures. All involved students of the RTG 2467 contributed specific parts to the final manuscript. All authors give their consent for submission and publication of this manuscript.

Corresponding authors

Correspondence to Marcel Köhn, Andrea Sinz or Vladimir N. Uversky.

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Piersimoni, L., Abd el Malek, M., Bhatia, T. et al. Lighting up Nobel Prize-winning studies with protein intrinsic disorder. Cell. Mol. Life Sci. 79, 449 (2022). https://doi.org/10.1007/s00018-022-04468-y

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