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Atomic resolution dynamics of cohesive interactions in phase-separated Nup98 FG domains

Author

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  • Eszter E. Najbauer

    (Max Planck Institute for Multidisciplinary Sciences)

  • Sheung Chun Ng

    (Max Planck Institute for Multidisciplinary Sciences)

  • Christian Griesinger

    (Max Planck Institute for Multidisciplinary Sciences)

  • Dirk Görlich

    (Max Planck Institute for Multidisciplinary Sciences)

  • Loren B. Andreas

    (Max Planck Institute for Multidisciplinary Sciences)

Abstract

Cohesive FG domains assemble into a condensed phase forming the selective permeability barrier of nuclear pore complexes. Nanoscopic insight into fundamental cohesive interactions has long been hampered by the sequence heterogeneity of native FG domains. We overcome this challenge by utilizing an engineered perfectly repetitive sequence and a combination of solution and magic angle spinning NMR spectroscopy. We map the dynamics of cohesive interactions in both phase-separated and soluble states at atomic resolution using TROSY for rotational correlation time (TRACT) measurements. We find that FG repeats exhibit nanosecond-range rotational correlation times and remain disordered in both states, although FRAP measurements show slow translation of phase-separated FG domains. NOESY measurements enable the direct detection of contacts involved in cohesive interactions. Finally, increasing salt concentration and temperature enhance phase separation and decrease local mobility of FG repeats. This lower critical solution temperature (LCST) behaviour indicates that cohesive interactions are driven by entropy.

Suggested Citation

  • Eszter E. Najbauer & Sheung Chun Ng & Christian Griesinger & Dirk Görlich & Loren B. Andreas, 2022. "Atomic resolution dynamics of cohesive interactions in phase-separated Nup98 FG domains," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28821-8
    DOI: 10.1038/s41467-022-28821-8
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    References listed on IDEAS

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    2. Franck Delavoie & Vanessa Soldan & Dana Rinaldi & Jean-Yves Dauxois & Pierre-Emmanuel Gleizes, 2019. "The path of pre-ribosomes through the nuclear pore complex revealed by electron tomography," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    3. Sheung Chun Ng & Thomas Güttler & Dirk Görlich, 2021. "Recapitulation of selective nuclear import and export with a perfectly repeated 12mer GLFG peptide," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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    Cited by:

    1. Sheung Chun Ng & Abin Biswas & Trevor Huyton & Jürgen Schünemann & Simone Reber & Dirk Görlich, 2023. "Barrier properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Alain Ibáñez de Opakua & Christian F. Pantoja & Maria-Sol Cima-Omori & Christian Dienemann & Markus Zweckstetter, 2024. "Impact of distinct FG nucleoporin repeats on Nup98 self-association," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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