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Atomic resolution dynamics of cohesive interactions in phase-separated Nup98 FG domains

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Najbauer,  E. E.
Research Group of Solid State NMR Spectroscopy-2, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

Ng,  S. C.
Department of Cellular Logistics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Griesinger,  C.
Department of NMR Based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

Görlich,  Dirk
Department of Cellular Logistics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Andreas,  L. B.
Research Group of Solid State NMR Spectroscopy-2, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Citation

Najbauer, E. E., Ng, S. C., Griesinger, C., Görlich, D., & Andreas, L. B. (2022). Atomic resolution dynamics of cohesive interactions in phase-separated Nup98 FG domains. Nature Communications, 13: 1494. doi:10.1038/s41467-022-28821-8.


Cite as: http://hdl.handle.net/21.11116/0000-000A-B0BA-D
Abstract
Cohesive FG domains assemble into a condensed phase forming the selective permeability barrier of nuclear pore complexes. Nanoscopic insight into fundamental cohesive interactions has long been hampered by the sequence heterogeneity of native FG domains. We overcome this challenge by utilizing an engineered perfectly repetitive sequence and a combination of solution and magic angle spinning NMR spectroscopy. We map the dynamics of cohesive interactions in both phase-separated and soluble states at atomic resolution using TROSY for rotational correlation time (TRACT) measurements. We find that FG repeats exhibit nanosecond-range rotational correlation times and remain disordered in both states, although FRAP measurements show slow translation of phase-separated FG domains. NOESY measurements enable the direct detection of contacts involved in cohesive interactions. Finally, increasing salt concentration and temperature enhance phase separation and decrease local mobility of FG repeats. This lower critical solution temperature (LCST) behaviour indicates that cohesive interactions are driven by entropy.