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000165219 0247_ $$2doi$$a10.1038/s41557-022-01035-7
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000165219 1001_ $$0P:(DE-2719)2812657$$aIbanez de Opakua, Alain$$b0$$eFirst author$$udzne
000165219 245__ $$aMolecular interactions of FG nucleoporin repeats at high resolution.
000165219 260__ $$aLondon$$bNature Publishing Group$$c2022
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000165219 520__ $$aProteins 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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000165219 650_7 $$2NLM Chemicals$$aNuclear Pore Complex Proteins
000165219 650_7 $$047E5O17Y3R$$2NLM Chemicals$$aPhenylalanine
000165219 650_7 $$2NLM Chemicals$$aNup98 protein, human
000165219 650_2 $$2MeSH$$aHumans
000165219 650_2 $$2MeSH$$aCryoelectron Microscopy
000165219 650_2 $$2MeSH$$aNuclear Pore: chemistry
000165219 650_2 $$2MeSH$$aNuclear Pore: metabolism
000165219 650_2 $$2MeSH$$aNuclear Pore Complex Proteins: genetics
000165219 650_2 $$2MeSH$$aNuclear Pore Complex Proteins: analysis
000165219 650_2 $$2MeSH$$aNuclear Pore Complex Proteins: chemistry
000165219 650_2 $$2MeSH$$aPhenylalanine: chemistry
000165219 650_2 $$2MeSH$$aRepetitive Sequences, Amino Acid
000165219 7001_ $$00000-0003-3378-0683$$aGeraets, James A$$b1
000165219 7001_ $$aFrieg, Benedikt$$b2
000165219 7001_ $$aDienemann, Christian$$b3
000165219 7001_ $$0P:(DE-2719)2811715$$aSavastano, Adriana$$b4$$udzne
000165219 7001_ $$0P:(DE-2719)9001085$$aRankovic, Marija$$b5$$udzne
000165219 7001_ $$00000-0002-5624-2477$$aCima-Omori, Maria-Sol$$b6
000165219 7001_ $$00000-0003-1803-5431$$aSchröder, Gunnar F$$b7
000165219 7001_ $$0P:(DE-2719)2810591$$aZweckstetter, Markus$$b8$$eLast author$$udzne
000165219 773__ $$0PERI:(DE-600)2464596-5$$a10.1038/s41557-022-01035-7$$gVol. 14, no. 11, p. 1278 - 1285$$n11$$p1278 - 1285$$tNature chemistry$$v14$$x1755-4330$$y2022
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