8CI8

Cryo-EM structure of the Nup98(298-327) fibril

Summary for 8CI8

• Entry DOI: 10.2210/pdb8ci8/pdb
• EMDB information: 16671
• Descriptor: Nuclear pore complex protein Nup98 (1 entity in total)
• Functional Keywords: nup98, nuclear pore, fg repeats, amyloid fibrils, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 25
• Total formula weight: 75856.78

Authors

Ibanez de Opakua, A.,Cima-Omori, S.,Dienemann, C.,Zweckstetter, M. (deposition date: 2023-02-09, release date: 2024-02-21, Last modification date: 2024-05-22)

Primary citation

Ibanez de Opakua, A.,Pantoja, C.F.,Cima-Omori, M.S.,Dienemann, C.,Zweckstetter, M.
Impact of distinct FG nucleoporin repeats on Nup98 self-association.
Nat Commun, 15:3797-3797, 2024

PubMed 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.

PubMed: 38714656
DOI: 10.1038/s41467-024-48194-4

Experimental method

ELECTRON MICROSCOPY (2.67 Å)