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Impact of distinct FG nucleoporin repeats on Nup98 self-association

Author

Listed:
  • Alain Ibáñez de Opakua

    (German Center for Neurodegenerative Diseases (DZNE))

  • Christian F. Pantoja

    (German Center for Neurodegenerative Diseases (DZNE))

  • Maria-Sol Cima-Omori

    (German Center for Neurodegenerative Diseases (DZNE))

  • Christian Dienemann

    (Department of Molecular Biology)

  • Markus Zweckstetter

    (German Center for Neurodegenerative Diseases (DZNE)
    Department of NMR-based Structural Biology)

Abstract

Nucleoporins rich in phenylalanine/glycine (FG) residues form the permeability barrier within the nuclear pore complex and are implicated in several pathological cellular processes, including oncogenic fusion condensates. The self-association of FG-repeat proteins and interactions between FG-repeats play a critical role in these activities by forming hydrogel-like structures. Here we show that mutation of specific FG repeats of Nup98 can strongly decrease the protein’s self-association capabilities. We further present a cryo-electron microscopy structure of a Nup98 peptide fibril with higher stability per residue compared with previous Nup98 fibril structures. The high-resolution structure reveals zipper-like hydrophobic patches which contain a GLFG motif and are less compatible for binding to nuclear transport receptors. The identified distinct molecular properties of different regions of the nucleoporin may contribute to spatial variations in the self-association of FG-repeats, potentially influencing transport processes through the nuclear pore.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48194-4
    DOI: 10.1038/s41467-024-48194-4
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    2. 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.
    3. Jeong Hyun Ahn & Eric S. Davis & Timothy A. Daugird & Shuai Zhao & Ivana Yoseli Quiroga & Hidetaka Uryu & Jie Li & Aaron J. Storey & Yi-Hsuan Tsai & Daniel P. Keeley & Samuel G. Mackintosh & Ricky D. , 2021. "Phase separation drives aberrant chromatin looping and cancer development," Nature, Nature, vol. 595(7868), pages 591-595, July.
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