Nup98 FG domains from diverse species spontaneously phase-separate into particles with nuclear pore-like permselectivity

Schmidt, Hermann Broder; Görlich, Dirk

doi:10.7554/elife.04251

Cited by 313 publications

(443 citation statements)

References 84 publications

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“…Nuclear pore complexes possess high frequency, weakly interacting FG motifs in disordered regions, yet exhibit long recovery times in FRAP experiments [144]. What needs to be considered is that repetitive motifs or SLiMs may generate a variety of contact topologies, resulting in large numbers of iso-energetic microstates and higher entropy.…”

Section: Figurementioning

confidence: 99%

Protein Phase Separation: A New Phase in Cell Biology

Boeynaems

Alberti

Fawzi

et al. 2018

Trends in Cell Biology

1,711

1,517

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Cellular compartments and organelles organize biological matter. Most well-known organelles are separated by a membrane boundary from their surrounding milieu. There are also many so-called membraneless organelles and recent studies suggest that these organelles, which are supramolecular assemblies of proteins and RNA molecules, form via protein phase separation. Recent discoveries have shed light on the molecular properties, formation, regulation, and function of membraneless organelles. A combination of techniques from cell biology, biophysics, physical chemistry, structural biology, and bioinformatics are starting to help establish the molecular principles of an emerging field, thus paving the way for exciting discoveries, including novel therapeutic approaches for the treatment of age-related disorders.

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Section: Figurementioning

confidence: 99%

Protein Phase Separation: A New Phase in Cell Biology

Boeynaems

Alberti

Fawzi

et al. 2018

Trends in Cell Biology

1,711

1,517

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“…Experiments in Xenopus egg extracts and yeast point to a primary role for a subgroup of FG-repeats enriched in GLFG motifs in establishing the diffusion barrier (Hulsmann et al, 2012; Timney et al, 2016). The GLFG-containing repeats display cohesive properties and can form aggregates with NPC-like selectivity in vitro (Schmidt and Gorlich, 2015a). Although several models for NPC selectivity have been proposed (Lim et al, 2007; Ribbeck and Gorlich, 2002; Rout et al, 2003), it is still unclear how FG-repeats determine the remarkable permeability properties of the NPC.…”

Section: Introductionmentioning

confidence: 99%

“…This was also observed for human Nup93 (Xu and Powers, 2013) and for the orthologues of Nup188 and Nup192 from thermophilic fungi (Andersen et al, 2013b). However, the functional significance of these interactions remained unclear (Andersen et al, 2013b; Hurt and Beck, 2015; Schmidt and Gorlich, 2015a, b). …”

Section: Introductionmentioning

confidence: 99%

Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex

Onischenko

Tang

Andersen

et al. 2017

Cell

110

100

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Summary Nuclear pore complexes (NPCs) are ~100 MDa transport channels assembled from multiple copies of ~30 nucleoporins (Nups). One third of these Nups contain phenylalanine-glycine (FG)-rich repeats forming a diffusion barrier, which is selectively permeable for nuclear transport receptors that interact with these repeats. Here, we identify an additional function of FG-repeats in the structure and biogenesis of the yeast NPC. We demonstrate that GLFG-containing FG-repeats directly bind to multiple scaffold Nups in vitro and act as NPC targeting determinants in vivo. Furthermore, we show that the GLFG repeats of Nup116 function in a redundant manner with Nup188, a non-essential scaffold Nup, to stabilize critical interactions within the NPC scaffold needed for late steps of NPC assembly. Our results reveal a previously unanticipated structural role for natively unfolded GLFG-repeats as velcro to link NPC subcomplexes, and thus add a new layer of connections to current models of the NPC architecture.

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“…This is straightforward to explain by an adaptive barrier that seals around a translocating species; in particular as cohesive FG domains readily assemble such self-sealing barriers in the form of FG hydrogels (28,29).…”

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confidence: 99%

Crystal structure of the metazoan Nup62•Nup58•Nup54 nucleoporin complex

Chug

Trakhanov

Hülsmann

et al. 2015

Science

Self Cite

111

130

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Nuclear pore complexes (NPCs) conduct nucleocytoplasmic transport and gain transport selectivity through nucleoporin FG domains. Here, we report a structural analysis of the FG Nup62•58•54 complex, which is a crucial component of the transport system. It comprises a ≈13 nanometer-long trimerization interface with an unusual 2W3F coil, a canonical heterotrimeric coiled coil, and a kink that enforces a compact six-helix bundle. Nup54 also contains a ferredoxin-like domain. We further identified a heterotrimeric Nup93-binding module for NPC anchorage. The quaternary structure alternations in the Nup62 complex, which were previously proposed to trigger a general gating of the NPC, are incompatible with the trimer structure. We suggest that the highly elongated Nup62 complex projects barrier-forming FG repeats far into the central NPC channel, supporting a barrier that guards the entire cross section.

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Nup98 FG domains from diverse species spontaneously phase-separate into particles with nuclear pore-like permselectivity

Cited by 313 publications

References 84 publications

Protein Phase Separation: A New Phase in Cell Biology

Protein Phase Separation: A New Phase in Cell Biology

Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex

Crystal structure of the metazoan Nup62•Nup58•Nup54 nucleoporin complex

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