Dissecting the biophysics and biology of intrinsically disordered proteins

doi:10.1016/j.tibs.2023.10.002

. 2024 Feb;49(2):101-104.

doi: 10.1016/j.tibs.2023.10.002. Epub 2023 Nov 8.

Dissecting the biophysics and biology of intrinsically disordered proteins

Priya R Banerjee¹, Alex S Holehouse², Richard Kriwacki³, Paul Robustelli⁴, Hao Jiang⁵, Alexander I Sobolevsky⁶, Jennifer M Hurley⁷, Joshua T Mendell⁸

Affiliations

¹ Department of Physics, University at Buffalo, NY 14260, USA. Electronic address: prbanerj@buffalo.edu.
² Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO, USA.
³ Structural Biology Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
⁴ Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
⁵ Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22903, USA.
⁶ Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
⁷ Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
⁸ UT Southwestern Medical Center and Howard Hughes Medical Institute, Dallas, TX 75390, USA.

PMID: 37949765
PMCID: PMC10872967
DOI: 10.1016/j.tibs.2023.10.002

Dissecting the biophysics and biology of intrinsically disordered proteins

Priya R Banerjee et al. Trends Biochem Sci. 2024 Feb.

. 2024 Feb;49(2):101-104.

doi: 10.1016/j.tibs.2023.10.002. Epub 2023 Nov 8.

Authors

Priya R Banerjee¹, Alex S Holehouse², Richard Kriwacki³, Paul Robustelli⁴, Hao Jiang⁵, Alexander I Sobolevsky⁶, Jennifer M Hurley⁷, Joshua T Mendell⁸

Affiliations

¹ Department of Physics, University at Buffalo, NY 14260, USA. Electronic address: prbanerj@buffalo.edu.
² Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO, USA.
³ Structural Biology Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
⁴ Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
⁵ Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22903, USA.
⁶ Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
⁷ Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
⁸ UT Southwestern Medical Center and Howard Hughes Medical Institute, Dallas, TX 75390, USA.

PMID: 37949765
PMCID: PMC10872967
DOI: 10.1016/j.tibs.2023.10.002

Abstract

Intrinsically disordered regions (IDRs) within human proteins play critical roles in cellular information processing, including signaling, transcription, stress response, DNA repair, genome organization, and RNA processing. Here, we summarize current challenges in the field and propose cutting-edge approaches to address them in physiology and disease processes, with a focus on cancer.

Keywords: cancer; condensates; phase separation; single-molecule microscopy.

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Conflict of interest statement

Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Figure 1:**
Emerging paradigm and current challenges in sequence-ensemble-function relationships of intrinisically disordered proteins.

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References

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1. Forman-Kay Julie D and Mittag T (2013) From Sequence and Forces to Structure, Function, and Evolution of Intrinsically Disordered Proteins. Structure 21:1492–1499. doi: 10.1016/j.str.2013.08.001 - DOI - PMC - PubMed
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[1] Alberti S, Gladfelter A and Mittag T (2019) Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates. Cell 176:419–434. doi: 10.1016/j.cell.2018.12.035 - DOI - PMC - PubMed

[2] Alberti S, Gladfelter A and Mittag T (2019) Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates. Cell 176:419–434. doi: 10.1016/j.cell.2018.12.035 - DOI - PMC - PubMed

[3] Boija A, Klein IA and Young RA (2021) Biomolecular Condensates and Cancer. Cancer Cell 39:174–192. doi: 10.1016/j.ccell.2020.12.003 - DOI - PMC - PubMed

[4] Boija A, Klein IA and Young RA (2021) Biomolecular Condensates and Cancer. Cancer Cell 39:174–192. doi: 10.1016/j.ccell.2020.12.003 - DOI - PMC - PubMed

[5] Shirnekhi HK, Chandra B and Kriwacki RW (2023) The Role of Phase-Separated Condensates in Fusion Oncoprotein–Driven Cancers. Annual Review of Cancer Biology 7:73–91. doi: 10.1146/annurev-cancerbio-061421-122050 - DOI

[6] Shirnekhi HK, Chandra B and Kriwacki RW (2023) The Role of Phase-Separated Condensates in Fusion Oncoprotein–Driven Cancers. Annual Review of Cancer Biology 7:73–91. doi: 10.1146/annurev-cancerbio-061421-122050 - DOI

[7] Forman-Kay Julie D and Mittag T (2013) From Sequence and Forces to Structure, Function, and Evolution of Intrinsically Disordered Proteins. Structure 21:1492–1499. doi: 10.1016/j.str.2013.08.001 - DOI - PMC - PubMed

[8] Forman-Kay Julie D and Mittag T (2013) From Sequence and Forces to Structure, Function, and Evolution of Intrinsically Disordered Proteins. Structure 21:1492–1499. doi: 10.1016/j.str.2013.08.001 - DOI - PMC - PubMed

[9] Hultqvist G, Åberg E, Camilloni C, Sundell GN, Andersson E, Dogan J, Chi CN, Vendruscolo M and Jemth P (2017) Emergence and evolution of an interaction between intrinsically disordered proteins. eLife 6:e16059. doi: 10.7554/eLife.16059 - DOI - PMC - PubMed

[10] Hultqvist G, Åberg E, Camilloni C, Sundell GN, Andersson E, Dogan J, Chi CN, Vendruscolo M and Jemth P (2017) Emergence and evolution of an interaction between intrinsically disordered proteins. eLife 6:e16059. doi: 10.7554/eLife.16059 - DOI - PMC - PubMed

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Dissecting the biophysics and biology of intrinsically disordered proteins

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Dissecting the biophysics and biology of intrinsically disordered proteins

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