ジャーナル: Nat Chem / 年: 2022 タイトル: Molecular interactions of FG nucleoporin repeats at high resolution. 著者: Alain Ibáñez de Opakua / James A Geraets / Benedikt Frieg / Christian Dienemann / Adriana Savastano / Marija Rankovic / Maria-Sol Cima-Omori / Gunnar F Schröder / Markus Zweckstetter / 要旨: 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 ...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.
名称: Cryo-em structure of the Nup98 fibril polymorph 3 / タイプ: COMPLEX 詳細: The Nup98 polymorph 3 fibril is formed by two protofilaments, consisting of Nup98 monomers. Entity ID: all / 由来: RECOMBINANT
分子量
実験値: NO
由来(天然)
生物種: Homo sapiens (ヒト)
由来(組換発現)
生物種: Escherichia coli BL21(DE3) (大腸菌)
緩衝液
pH: 7
緩衝液成分
ID
単位
Buffer-ID
1
mM
1
2
mM
1
3
%
1
試料
包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES
急速凍結
装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 293 K