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Molecular interactions of FG nucleoporin repeats at high resolution
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 o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630130/ https://www.ncbi.nlm.nih.gov/pubmed/36138110 http://dx.doi.org/10.1038/s41557-022-01035-7 |
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author | Ibáñez de Opakua, Alain Geraets, James A. Frieg, Benedikt Dienemann, Christian Savastano, Adriana Rankovic, Marija Cima-Omori, Maria-Sol Schröder, Gunnar F. Zweckstetter, Markus |
author_facet | Ibáñez de Opakua, Alain Geraets, James A. Frieg, Benedikt Dienemann, Christian Savastano, Adriana Rankovic, Marija Cima-Omori, Maria-Sol Schröder, Gunnar F. Zweckstetter, Markus |
author_sort | Ibáñez de Opakua, Alain |
collection | PubMed |
description | 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. [Image: see text] |
format | Online Article Text |
id | pubmed-9630130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96301302022-11-04 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 Nat Chem Article 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. [Image: see text] Nature Publishing Group UK 2022-09-22 2022 /pmc/articles/PMC9630130/ /pubmed/36138110 http://dx.doi.org/10.1038/s41557-022-01035-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ibáñez de Opakua, Alain Geraets, James A. Frieg, Benedikt Dienemann, Christian Savastano, Adriana Rankovic, Marija Cima-Omori, Maria-Sol Schröder, Gunnar F. Zweckstetter, Markus Molecular interactions of FG nucleoporin repeats at high resolution |
title | Molecular interactions of FG nucleoporin repeats at high resolution |
title_full | Molecular interactions of FG nucleoporin repeats at high resolution |
title_fullStr | Molecular interactions of FG nucleoporin repeats at high resolution |
title_full_unstemmed | Molecular interactions of FG nucleoporin repeats at high resolution |
title_short | Molecular interactions of FG nucleoporin repeats at high resolution |
title_sort | molecular interactions of fg nucleoporin repeats at high resolution |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630130/ https://www.ncbi.nlm.nih.gov/pubmed/36138110 http://dx.doi.org/10.1038/s41557-022-01035-7 |
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