Super-resolution 3D tomography of interactions and competition in the nuclear pore complex

Ma, Junjun; Goryaynov, Alexander; Yang, Weidong

doi:10.1038/nsmb.3174

Cited by 62 publications

(100 citation statements)

References 46 publications

(81 reference statements)

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“…1 C-D). This map covers the majority of FG-domains of all native FG-Nups since this spatial distribution of the FG-domains agrees well with the full spectrum of the distribution of all FG-Nups in vivo obtained by SPEED microscopy [71][72][73][74][75] (Fig. 1).…”

Section: The Native Conformation Of the Fg-nups Barrier In The Npcssupporting

confidence: 83%

“…75 We found that these maps have fundamental similarities, suggesting that these different probes may largely bind to same groups of FG-domains or recognize almost all the available FG-domains in the native NPCs. Finally, a complete super-resolution 3D-map of the native configuration of FG-domains in the native NPCs was obtained by merging the above 3 integrated 3D-tomographies from all 3 sets 75 ( Fig. 1).…”

Section: The Native Conformation Of the Fg-nups Barrier In The Npcsmentioning

confidence: 76%

“…38 Very recently, GLFG of yNup116 and hNup98, FxFG of hNup62, and FG of yNup42 were all found to interact in vivo with many FG-Nups of native human NPCs. 75 The data from mutated FG-domains further suggest that LF motifs in GLFG and the overall hydrophobicity are required for the interactions. 19 Molecular simulation studies suggest that the backbone-backbone hydrogen bonding also contributes to the interactions of FG-Nups, and hydrophilic linkers may further strengthen the interactions in forming the stabilized permeability barrier.…”

Section: Interactions Among Fg-nups and Between Fg-nups And Ntrsmentioning

confidence: 95%

“…Evidently, the spatial distribution of the interactions between FG-Nups in the native NPCs, as recently determined by singlepoint edge-extraction sub-diffraction (SPEED) microscopy, suggests that not all the individual FGNups interact with each other in vivo, and certain FGNups are indeed non-interacting FG-Nups. 75 Finally, whether FG-Nups are interacting or noninteracting is an important question in considering how and where the permeability barrier is formed. Caution must be exercised in interpreting the data from the above assays.…”

Section: Non-interacting Fg-nupsmentioning

confidence: 99%

“…Recently we accomplished the task by first mapping the spatial locations of FG-FG and FG-NTRs interaction sites in native NPCs with high-speed super-resolution SPEED microscopy. [72][73][74][75] Then we reconstructed these interactions to form the complete map of the FG-Nup barrier.…”

Section: The Native Conformation Of the Fg-nups Barrier In The Npcsmentioning

confidence: 99%

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The selective permeability barrier in the nuclear pore complex

Goryaynov

Yang

2016

Nucleus

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The nuclear pore complex (NPC) mediates the shuttle transport of macromolecules between the nucleus and cytoplasm in eukaryotic cells. The permeability barrier formed by intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG-Nups) in the NPC functions as the critical selective control for nucleocytoplasmic transport. Signal-independent small molecules (< 40 kDa) passively diffuse through the pore, but passage of large cargo molecules is inhibited unless they are chaperoned by nuclear transport receptors (NTRs). NTRs are capable of interacting with FG-Nups and guide the cargos to cross the barrier by facilitated diffusion. The native conformation of the FGNups permeability barrier and the competition among multiple NTRs interacting with this barrier in the native NPCs are the 2 core questions still being highly debated in the field. Recently, we applied high-speed super-resolution fluorescence microscopy to map out the natural structure of the FGNups barrier and determined the competition among multiple NTRs as they interact with the barrier in the native NPCs. In this extra-view article, we will review the current understanding in the configuration and function of FG-Nups barrier and highlight the new evidence obtained recently to answer the core questions in nucleocytoplasmic transport.

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Section: The Native Conformation Of the Fg-nups Barrier In The Npcssupporting

confidence: 83%

Section: The Native Conformation Of the Fg-nups Barrier In The Npcsmentioning

confidence: 76%

Section: Interactions Among Fg-nups and Between Fg-nups And Ntrsmentioning

confidence: 95%

Section: Non-interacting Fg-nupsmentioning

confidence: 99%

Section: The Native Conformation Of the Fg-nups Barrier In The Npcsmentioning

confidence: 99%

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The selective permeability barrier in the nuclear pore complex

Goryaynov

Yang

2016

Nucleus

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Nucleocytoplasmic transport of intrinsically disordered proteins studied by high‐speed super‐resolution microscopy

Junod

Kelich²,

Ma³

et al. 2020

Protein Science

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Both natively folded and intrinsically disordered proteins (IDPs) destined for the nucleus need to transport through the nuclear pore complexes (NPCs) in eukaryotic cells. NPCs allow for passive diffusion of small folded proteins while barricading large ones, unless they are facilitated by nuclear transport receptors. However, whether nucleocytoplasmic transport of IDPs would follow these rules remains unknown. By using a high-speed super-resolution fluorescence microscopy, we have measured transport kinetics and 3D spatial locations of transport routes through native NPCs for various IDPs. Our data revealed that the rules executed for folded proteins are not well followed by the IDPs. Instead, both large and small IDPs can passively diffuse through the NPCs. Furthermore, their diffusion efficiencies and routes are differentiated by their content ratio of charged (Ch) and hydrophobic (Hy) amino acids. A Ch/Hy-ratio mechanism was finally suggested for nucleocytoplasmic transport of IDPs. K E Y W O R D Sintrinsically disordered proteins (IDPs), nuclear pore complex (NPC), nucleocytoplasmic transport, super-resolution Note: Disorder level score was calculated using IUPRED. 58 Approximately 500-1,200 spatial locations were collected in order to obtain reliable 3D spatial transport route for each candidate in our measurements based on computation simulation (Section 4). Abbreviations: Ch/Hy, charged/hydrophobic; CREST, calcium-responsive transactivator; IDP, intrinsically disordered protein; IUPRED, intrinsically unstructured proteins prediction.

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Structure and Function of the Nuclear Pore Complex Revealed by High-Resolution Fluorescence Microscopy

Kelich

Yang

2018

Nucleic Acids and Molecular Biology

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Super-resolution 3D tomography of interactions and competition in the nuclear pore complex

Cited by 62 publications

References 46 publications

The selective permeability barrier in the nuclear pore complex

The selective permeability barrier in the nuclear pore complex

Nucleocytoplasmic transport of intrinsically disordered proteins studied by high‐speed super‐resolution microscopy

Structure and Function of the Nuclear Pore Complex Revealed by High-Resolution Fluorescence Microscopy

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