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http://doi.org/10.25358/openscience-9682
Autoren: | Yu, Miao Heidari, Maziar Mikhaleva, Sofya Tan, Piau Siong Mingu, Sara Ruan, Hao Reinkemeier, Christopher D. Obarska-Kosinska, Agnieszka Siggel, Marc Beck, Martin Hummer, Gerhard Lemke, Edward A. |
Titel: | Visualizing the disordered nuclear transport machinery in situ |
Online-Publikationsdatum: | 21-Nov-2023 |
Erscheinungsdatum: | 2023 |
Sprache des Dokuments: | Englisch |
Zusammenfassung/Abstract: | The approximately 120 MDa mammalian nuclear pore complex (NPC) acts as a gatekeeper for the transport between the nucleus and cytosol1. The central channel of the NPC is filled with hundreds of intrinsically disordered proteins (IDPs) called FG-nucleoporins (FG-NUPs)2,3. Although the structure of the NPC scaffold has been resolved in remarkable detail, the actual transport machinery built up by FG-NUPs—about 50 MDa—is depicted as an approximately 60-nm hole in even highly resolved tomograms and/or structures computed with artificial intelligence4,5,6,7,8,9,10,11. Here we directly probed conformations of the vital FG-NUP98 inside NPCs in live cells and in permeabilized cells with an intact transport machinery by using a synthetic biology-enabled site-specific small-molecule labelling approach paired with highly time-resolved fluorescence microscopy. Single permeabilized cell measurements of the distance distribution of FG-NUP98 segments combined with coarse-grained molecular simulations of the NPC allowed us to map the uncharted molecular environment inside the nanosized transport channel. We determined that the channel provides—in the terminology of the Flory polymer theory12—a ‘good solvent’ environment. This enables the FG domain to adopt expanded conformations and thus control transport between the nucleus and cytoplasm. With more than 30% of the proteome being formed from IDPs, our study opens a window into resolving disorder–function relationships of IDPs in situ, which are important in various processes, such as cellular signalling, phase separation, ageing and viral entry. |
DDC-Sachgruppe: | 570 Biowissenschaften 570 Life sciences |
Veröffentlichende Institution: | Johannes Gutenberg-Universität Mainz |
Organisationseinheit: | FB 10 Biologie |
Veröffentlichungsort: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-9682 |
Version: | Published version |
Publikationstyp: | Zeitschriftenaufsatz |
Weitere Angaben zur Dokumentart: | Scientific article |
Nutzungsrechte: | CC BY |
Informationen zu den Nutzungsrechten: | https://creativecommons.org/licenses/by/4.0/ |
Zeitschrift: | Nature 617 |
Seitenzahl oder Artikelnummer: | 162 169 |
Verlag: | Nature Publ. Group |
Verlagsort: | London u.a. |
Erscheinungsdatum: | 2023 |
ISSN: | 1476-4687 0028-0836 |
DOI der Originalveröffentlichung: | 10.1038/s41586-023-05990-0 |
Enthalten in den Sammlungen: | JGU-Publikationen |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | ||
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visualizing_the_disordered_nu-20231120095159488.pdf | Visualizing the disordered nuclear transport machinery in situ | 12.45 MB | Adobe PDF | Öffnen/Anzeigen |