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Molecular interactions of FG nucleoporin repeats at high resolution.
Ibáñez de Opakua, Alain; Geraets, James A; Frieg, Benedikt; Dienemann, Christian; Savastano, Adriana; Rankovic, Marija; Cima-Omori, Maria-Sol; Schröder, Gunnar F; Zweckstetter, Markus.
Afiliação
  • Ibáñez de Opakua A; German Center for Neurodegenerative Diseases, Göttingen, Germany.
  • Geraets JA; Institute of Biological Information Processing (Structural Biochemistry), Forschungszentrum Jülich GmbH, Jülich, Germany.
  • Frieg B; Institute of Biological Information Processing (Structural Biochemistry), Forschungszentrum Jülich GmbH, Jülich, Germany.
  • Dienemann C; Max Planck Institute for Multidisciplinary Sciences, Department of Molecular Biology, Göttingen, Germany.
  • Savastano A; German Center for Neurodegenerative Diseases, Göttingen, Germany.
  • Rankovic M; Max Planck Institute for Multidisciplinary Sciences, Department of NMR-based Structural Biology, Göttingen, Germany.
  • Cima-Omori MS; German Center for Neurodegenerative Diseases, Göttingen, Germany.
  • Schröder GF; Institute of Biological Information Processing (Structural Biochemistry), Forschungszentrum Jülich GmbH, Jülich, Germany. gu.schroeder@fz-juelich.de.
  • Zweckstetter M; Physics Department, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. gu.schroeder@fz-juelich.de.
Nat Chem ; 14(11): 1278-1285, 2022 11.
Article em En | MEDLINE | ID: mdl-36138110
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 ß-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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Poro Nuclear / Complexo de Proteínas Formadoras de Poros Nucleares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Poro Nuclear / Complexo de Proteínas Formadoras de Poros Nucleares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article