A simple thermodynamic description of phase separation of Nup98 FG domains

Ng, Sheung Chun; Görlich, Dirk

doi:10.1101/2022.07.26.501556

Cited by 2 publications

(5 citation statements)

References 119 publications

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“…The purified protein thus behaves like gelatin, even though the amino acid compositions of the two proteins are very different. This reversible thermosensitivity differs from that of the FG domain of the nucleoporin NUP98, whose phase separation is more favorable at higher temperatures ( 46 ). The difference might be due to hydrogen bonds between tyrosine hydroxyl groups contributing to the cohesion of the YG hydrogel.…”

Section: Yg Domains Form Hydrogelsmentioning

confidence: 98%

Protein import into peroxisomes occurs through a nuclear pore–like phase

Yuan

Skowyra

Feng

et al. 2022

Science

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Peroxisomes are ubiquitous organelles whose dysfunction causes fatal human diseases. Most peroxisomal proteins are imported from the cytosol in a folded state by the soluble receptor PEX5. How folded cargo crosses the membrane is unknown. Here, we show that peroxisomal import is similar to nuclear transport. The peroxisomal membrane protein PEX13 contains a conserved tyrosine (Y)– and glycine (G)–rich YG domain, which forms a selective phase resembling that formed by phenylalanine-glycine (FG) repeats within nuclear pores. PEX13 resides in the membrane in two orientations that oligomerize and suspend the YG meshwork within the lipid bilayer. Purified YG domains form hydrogels into which PEX5 selectively partitions, by using conserved aromatic amino acid motifs, bringing cargo along. The YG meshwork thus forms an aqueous conduit through which PEX5 delivers folded proteins into peroxisomes.

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Section: Yg Domains Form Hydrogelsmentioning

confidence: 98%

Protein import into peroxisomes occurs through a nuclear pore–like phase

Yuan

Skowyra

Feng

et al. 2022

Science

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“…2c) or the C sat : C dense ratio and the spacer length. The concentration ratio is also linearly related to the free energy change of phase separation 57 : where R is the gas constant (8.31 J/mol⋅K) and T the absolute temperature in Kelvin. ΔG thus depends inversely on the spacer length (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1; refs. 57,60 ). Increasing the salt concentration had an opposite effect, in particular for the long-spacer FG phases.…”

Section: Shorter Spacers Make the Fg Phase A Stricter Barriermentioning

confidence: 99%

“…2c) or the C sat : C dense ratio and the spacer length. The concentration ratio is also linearly related to the free energy change of phase separation 57 :…”

Section: Shorter Inter Fg Spacers Enhance Cohesive Interactionsmentioning

confidence: 99%

“…In fact, C sat here is so low that the soluble fraction remained undetectable in our phase separation experiments. C sat decreases exponentially with the number of repeats 57 , and even when reducing the number of FSFG x12 repeats from 52 to 29…”

Section: Antagonism Between Fg Cohesion and Ntr•fg Interactionsmentioning

confidence: 99%

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Barrier properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length

Ng¹,

Biswas

Huyton³

et al. 2022

Preprint

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Nup98 FG repeat domains comprise hydrophobic FG motifs linked through uncharged spacers. FG motifs capture nuclear transport receptors (NTRs) during nuclear pore complex (NPC) passage, confer inter-repeat cohesion, and condense the domains into a selective phase with NPC-typical barrier properties. We found that shortening inter-FG spacers enhances cohesion, increases phase density, and tightens such barrier – consistent with a sieve-like phase. Phase separation tolerated mutations of Nup98-typical GLFG motifs, provided the domain-hydrophobicity remained preserved. NTR-entry, however, was sensitive to (certain) deviations from canonical FG motifs, suggesting a co-evolutionary adaptation. Unexpectedly, we found that arginines promote efficient FG-phase entry also by means other than cation-π interactions. Although incompatible with NTR·cargo complexes, a YG phase displayed remarkable transport selectivity, particularly for evolved GFPNTR-variants. GLFG to FSFG mutations made the FG phase hypercohesive, precluding NTR-entry. Longer spacers relieved this hypercohesive phenotype. The antagonism between cohesion and NTR·FG interactions appears thus key to transport selectivity.

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A simple thermodynamic description of phase separation of Nup98 FG domains

Cited by 2 publications

References 119 publications

Protein import into peroxisomes occurs through a nuclear pore–like phase

Protein import into peroxisomes occurs through a nuclear pore–like phase

Barrier properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length

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