Barrier properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Barrier properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length
Ng, S. C.; Biswas, A.; Huyton, T.; Schünemann, J.; Reber, S. & Görlich, D. (2023)
Nature Communications, 14(1). DOI: https://doi.org/10.1038/s41467-023-36331-4
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Details
- Authors
- Ng, Sheung Chun; Biswas, Abin; Huyton, Trevor; Schünemann, Jürgen; Reber, Simone; Görlich, Dirk
- Abstract
- 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 GFP NTR -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.
- Issue Date
- 2023
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English