7Q65

Cryo-em structure of the Nup98 fibril polymorph 2

Summary for 7Q65

• Entry DOI: 10.2210/pdb7q65/pdb
• EMDB information: 13852
• Descriptor: Nuclear pore complex protein Nup98 (1 entity in total)
• Functional Keywords: nuclear pore complex protein nup98 functional amyloid fibril protein fibril, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 22
• Total formula weight: 88114.64

Authors

Ibanez de Opakua, A.,Geraets, J.A.,Frieg, B.,Dienemann, C.,Savastano, A.,Rankovic, M.,Cima-Omori, M.-S.,Schroeder, G.F.,Zweckstetter, M. (deposition date: 2021-11-05, release date: 2022-10-12, Last modification date: 2024-07-17)

Primary citation

Ibanez de Opakua, A.,Geraets, J.A.,Frieg, B.,Dienemann, C.,Savastano, A.,Rankovic, M.,Cima-Omori, M.S.,Schroder, G.F.,Zweckstetter, M.
Molecular interactions of FG nucleoporin repeats at high resolution.
Nat.Chem., 14:1278-1285, 2022

PubMed Abstract: Proteins that contain repeat phenylalanine-glycine (FG) residues phase separate into oncogenic transcription factor condensates in malignant leukaemias, form the permeability barrier of the nuclear pore complex and mislocalize in neurodegenerative diseases. Insights into the molecular interactions of FG-repeat nucleoporins have, however, remained largely elusive. Using a combination of NMR spectroscopy and cryoelectron microscopy, we have identified uniformly spaced segments of transient β-structure and a stable preformed α-helix recognized by messenger RNA export factors in the FG-repeat domain of human nucleoporin 98 (Nup98). In addition, we have determined at high resolution the molecular organization of reversible FG-FG interactions in amyloid fibrils formed by a highly aggregation-prone segment in Nup98. We have further demonstrated that amyloid-like aggregates of the FG-repeat domain of Nup98 have low stability and are reversible. Our results provide critical insights into the molecular interactions underlying the self-association and phase separation of FG-repeat nucleoporins in physiological and pathological cell activities.

PubMed: 36138110
DOI: 10.1038/s41557-022-01035-7

Experimental method

ELECTRON MICROSCOPY (3.32 Å)