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Barrier properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length

Author

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  • Sheung Chun Ng

    (Max Planck Institute for Multidisciplinary Sciences)

  • Abin Biswas

    (Humboldt-Universität zu Berlin
    Max Planck Institute for the Science of Light)

  • Trevor Huyton

    (Max Planck Institute for Multidisciplinary Sciences)

  • Jürgen Schünemann

    (Max Planck Institute for Multidisciplinary Sciences)

  • Simone Reber

    (Humboldt-Universität zu Berlin)

  • Dirk Görlich

    (Max Planck Institute for Multidisciplinary Sciences)

Abstract

Nup98 FG repeat domains comprise hydrophobic FG motifs linked through uncharged spacers. FG motifs capture nuclear transport receptors (NTRs) during nuclear pore complex (NPC) passage, confer inter-repeat cohesion, and condense the domains into a selective phase with NPC-typical barrier properties. We show that shortening inter-FG spacers enhances cohesion, increases phase density, and tightens such barrier - all consistent with a sieve-like phase. Phase separation tolerates mutating the Nup98-typical GLFG motifs, provided domain-hydrophobicity remains preserved. NTR-entry, however, is sensitive to (certain) deviations from canonical FG motifs, suggesting co-evolutionary adaptation. Unexpectedly, we observed that arginines promote FG-phase-entry apparently also by hydrophobic interactions/ hydrogen-bonding and not just through cation-π interactions. Although incompatible with NTR·cargo complexes, a YG phase displays remarkable transport selectivity, particularly for engineered GFPNTR-variants. GLFG to FSFG mutations make the FG phase hypercohesive, precluding NTR-entry. Extending spacers relaxes this hypercohesion. Thus, antagonism between cohesion and NTR·FG interactions is key to transport selectivity.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36331-4
    DOI: 10.1038/s41467-023-36331-4
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    References listed on IDEAS

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