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@ARTICLE{IbanezdeOpakua:165219,
author = {Ibanez de Opakua, Alain and Geraets, James A and Frieg,
Benedikt and Dienemann, Christian and Savastano, Adriana and
Rankovic, Marija and Cima-Omori, Maria-Sol and Schröder,
Gunnar F and Zweckstetter, Markus},
title = {{M}olecular interactions of {FG} nucleoporin repeats at
high resolution.},
journal = {Nature chemistry},
volume = {14},
number = {11},
issn = {1755-4330},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DZNE-2022-01516},
pages = {1278 - 1285},
year = {2022},
note = {CC BY: https://creativecommons.org/licenses/by/4.0/},
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.},
keywords = {Humans / Cryoelectron Microscopy / Nuclear Pore: chemistry
/ Nuclear Pore: metabolism / Nuclear Pore Complex Proteins:
genetics / Nuclear Pore Complex Proteins: analysis / Nuclear
Pore Complex Proteins: chemistry / Phenylalanine: chemistry
/ Repetitive Sequences, Amino Acid / Nuclear Pore Complex
Proteins (NLM Chemicals) / Phenylalanine (NLM Chemicals) /
Nup98 protein, human (NLM Chemicals)},
cin = {AG Zweckstetter},
ddc = {540},
cid = {I:(DE-2719)1410001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9630130},
pubmed = {pmid:36138110},
doi = {10.1038/s41557-022-01035-7},
url = {https://pub.dzne.de/record/165219},
}