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

Eszter E. Najbauer, Sheung Chun Ng, Christian Griesinger, Dirk Görlich () and Loren B. Andreas ()
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Eszter E. Najbauer: Max Planck Institute for Multidisciplinary Sciences
Sheung Chun Ng: Max Planck Institute for Multidisciplinary Sciences
Christian Griesinger: Max Planck Institute for Multidisciplinary Sciences
Dirk Görlich: Max Planck Institute for Multidisciplinary Sciences
Loren B. Andreas: Max Planck Institute for Multidisciplinary Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28821-8

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