TY  - JOUR
AU  - Ibáñez de Opakua, Alain
AU  - Geraets, James
AU  - Frieg, Benedikt
AU  - Dienemann, Christian
AU  - Savastano, Adriana
AU  - Rankovic, Marija
AU  - Cima-Omori, Maria-Sol
AU  - Schröder, Gunnar F.
AU  - Zweckstetter, Markus
TI  - Molecular interactions of FG nucleoporin repeats at high resolution
JO  - Nature chemistry
VL  - 14
IS  - 11
SN  - 1755-4330
CY  - London
PB  - Nature Publishing Group
M1  - FZJ-2022-05457
SP  - 1278 - 1285
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 36138110
UR  - <Go to ISI:>//WOS:000856606900001
DO  - DOI:10.1038/s41557-022-01035-7
UR  - https://juser.fz-juelich.de/record/912260
ER  -