A designer FG-Nup that reconstitutes the selective transport barrier of the nuclear pore complex

Fragasso, Alessio; Vries, Hendrik W. de; Andersson, John; Sluis, Eli O. van der; Giessen, E. van der; Dahlin, Andreas; Onck, Patrick; Dekker, Cees

doi:10.1038/s41467-021-22293-y

Cited by 49 publications

(73 citation statements)

References 78 publications

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“…NPCs control the movement of various proteins or biomolecules in and out of the nucleus based on the size 46 . This size-selective transport of large molecules through NPC were reported earlier 47,48 . The knowledge of the functioning and transport mechanism of the particles through the membrane channels like NPC has implications in cellular processes.…”

Section: Introductionsupporting

confidence: 82%

Transport of a self-propelled tracer through a hairy cylindrical channel: interplay of stickiness and activity

Sahoo,

Theeyancheri,

Chakrabarti

2022

Preprint

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Active transport of biomolecules assisted by motor proteins is imperative for the proper functioning of cellular activities. Inspired by the diffusion of active agents in crowded cellular channels, we computationally investigate the transport of an active tracer through a polymer grafted cylindrical channel by varying the activity of the tracer and stickiness of the tracer to the polymers. Our results reveal that the passive tracer exhibits profound subdiffusion with increasing stickiness by exploring deep into the grafted polymeric zone, while purely repulsive one prefers to diffuse through the pore-like space created along the cylindrical axis of the channel. In contrast, the active tracer shows faster dynamics and intermediate superdiffusion even though the tracer preferentially stays close to the dense polymeric region. This observation is further supported by the sharp peaks in the density profile of the probability of radial displacement of the tracer. We discover that the activity plays an important role in deciding the pathway that the tracer takes through the narrow channel. Interestingly, increasing the activity washes out the effect of stickiness. Adding to this, van-Hove functions manifest that the active tracer dynamics deviates from Gaussianity, and the degree of deviation grows with the activity. Our work has direct implications on how effective transportation and delivery of cargo can be achieved through a confined medium where activity, interactions, and crowding are interplaying. Looking ahead, these factors will be crucial for understanding the mechanism of artificial self-powered machines navigating through the cellular channels and performing in vivo challenging tasks.

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Section: Introductionsupporting

confidence: 82%

Transport of a self-propelled tracer through a hairy cylindrical channel: interplay of stickiness and activity

Sahoo,

Theeyancheri,

Chakrabarti

2022

Preprint

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“…Our bioinformatic analysis revealed that all orthologs of the NUP58 protein are also potential amyloids. We have also found a fragment which is amyloidogenic in many orthologs and located outside of the FG repeat region, which is supposed to play a key role in formation of selective barrier [40][41][42]. Notably, the conservation of the protein sequence in this fragment is lower than the conservation of amyloidogenic properties (Figure 1b).…”

Section: Human Nup58 Protein Demonstrates Amyloid Properties In C-dag Systemmentioning

confidence: 90%

The Human NUP58 Nucleoporin Can Form Amyloids In Vitro and In Vivo

et al. 2021

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Amyloids are fibrillar protein aggregates with a cross-β structure and unusual features, including high resistance to detergent or protease treatment. More than two hundred different proteins with amyloid or amyloid-like properties are already known. Several examples of nucleoporins (e.g., yeast Nup49, Nup100, Nup116, and human NUP153) are supposed to form amyloid fibrils. In this study, we demonstrated an ability of the human NUP58 nucleoporin to form amyloid aggregates in vivo and in vitro. Moreover, we found two forms of NUP58 aggregates: oligomers and polymers stabilized by disulfide bonds. Bioinformatic analysis revealed that all known orthologs of this protein are potential amyloids which possess several regions with conserved ability to aggregation. The biological role of nucleoporin amyloid formation is debatable. We suggest that it is a rather abnormal process, which is characteristic for many proteins implicated in phase separation.

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“…However, there is no ultrastructural evidence for a pore-associated structure at the nucleomorph membrane and the retention of these subunits may indicate recruitment to other processes. Secondly, attempts to create an artificial pore, using truncated versions of yeast Nsp1 and Nup100 [ 185 ] or a designer ‘NupX’ [ 186 ], produced pores with selective permeability, suggesting minimal requirements to achieve gating. A self-assembling pore of just two POMs, Ndc1 and an FG-containing Pom121 in a lipid bilayer has also been achieved [ 187 ].…”

Section: Npc Evolution: a Minimal Pore?mentioning

confidence: 99%

Evolution and diversification of the nuclear pore complex

Макаров

Padilla-Mejía

Field

2021

Biochemical Society Transactions

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The nuclear pore complex (NPC) is responsible for transport between the cytoplasm and nucleoplasm and one of the more intricate structures of eukaryotic cells. Typically composed of over 300 polypeptides, the NPC shares evolutionary origins with endo-membrane and intraflagellar transport system complexes. The modern NPC was fully established by the time of the last eukaryotic common ancestor and, hence, prior to eukaryote diversification. Despite the complexity, the NPC structure is surprisingly flexible with considerable variation between lineages. Here, we review diversification of the NPC in major taxa in view of recent advances in genomic and structural characterisation of plant, protist and nucleomorph NPCs and discuss the implications for NPC evolution. Furthermore, we highlight these changes in the context of mRNA export and consider how this process may have influenced NPC diversity. We reveal the NPC as a platform for continual evolution and adaptation.

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A designer FG-Nup that reconstitutes the selective transport barrier of the nuclear pore complex

Cited by 49 publications

References 78 publications

Transport of a self-propelled tracer through a hairy cylindrical channel: interplay of stickiness and activity

Transport of a self-propelled tracer through a hairy cylindrical channel: interplay of stickiness and activity

The Human NUP58 Nucleoporin Can Form Amyloids In Vitro and In Vivo

Evolution and diversification of the nuclear pore complex

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