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001     165219
005     20230915090612.0
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024 7 _ |a 10.1038/s41557-022-01035-7
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024 7 _ |a pmid:36138110
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024 7 _ |a 1755-4330
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037 _ _ |a DZNE-2022-01516
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100 1 _ |a Ibanez de Opakua, Alain
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245 _ _ |a Molecular interactions of FG nucleoporin repeats at high resolution.
260 _ _ |a London
|c 2022
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520 _ _ |a 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.
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650 _ 7 |a Nuclear Pore Complex Proteins
|2 NLM Chemicals
650 _ 7 |a Phenylalanine
|0 47E5O17Y3R
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650 _ 7 |a Nup98 protein, human
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Cryoelectron Microscopy
|2 MeSH
650 _ 2 |a Nuclear Pore: chemistry
|2 MeSH
650 _ 2 |a Nuclear Pore: metabolism
|2 MeSH
650 _ 2 |a Nuclear Pore Complex Proteins: genetics
|2 MeSH
650 _ 2 |a Nuclear Pore Complex Proteins: analysis
|2 MeSH
650 _ 2 |a Nuclear Pore Complex Proteins: chemistry
|2 MeSH
650 _ 2 |a Phenylalanine: chemistry
|2 MeSH
650 _ 2 |a Repetitive Sequences, Amino Acid
|2 MeSH
700 1 _ |a Geraets, James A
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700 1 _ |a Frieg, Benedikt
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700 1 _ |a Dienemann, Christian
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700 1 _ |a Savastano, Adriana
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700 1 _ |a Rankovic, Marija
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700 1 _ |a Cima-Omori, Maria-Sol
|0 0000-0002-5624-2477
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700 1 _ |a Schröder, Gunnar F
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700 1 _ |a Zweckstetter, Markus
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773 _ _ |a 10.1038/s41557-022-01035-7
|g Vol. 14, no. 11, p. 1278 - 1285
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|t Nature chemistry
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856 4 _ |u https://pub.dzne.de/record/165219/files/DZNE-2022-01516.pdf
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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