Conformational dynamics of the nuclear pore complex central channel

Biochemical Society Transactions, Год журнала: 2025, Номер 53(01)

Опубликована: Фев. 7, 2025

The nuclear pore complex (NPC) is a vital regulator of molecular transport between the nucleus and cytoplasm in eukaryotic cells. At heart NPC’s function are intrinsically disordered phenylalanineglycine-rich nucleoporins (FG-Nups), which form dynamic permeability barrier within central channel. This nature facilitates efficient nucleocytoplasmic but also poses significant challenges to its characterization, especially nano-confined environment NPC. Recent advances experimental techniques, such as cryo-electron microscopy, atomic force fluorescence magnetic resonance, along with computational modeling, have illuminated conformational flexibility FG-Nups, underpins their functional versatility. review synthesizes these advancements, emphasizing how disruptions FG-Nup behavior—caused by mutations or pathological interactions—contribute diseases neurodegenerative disorders, aging-related decline, viral infections. Despite progress, persist deciphering dynamics crowded cellular environment, under conditions. Addressing gaps critical for advancing therapeutic strategies targeting NPC dysfunction disease progression.

Язык: Английский

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On the Significance of the Terminal Location of Prion-Forming Regions of Yeast Proteins

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1637 - 1637

Опубликована: Фев. 14, 2025

The prion-forming regions (PFRs) of yeast prion proteins are usually located at either the N- or C-terminus a protein. In Sup35 prion, main structure contains 71 N-terminal residues. Here, we investigated importance terminal PFR location for properties. Two prionogenic sequences 29 and 30 residues two random 23 15 were added to N-terminus, making original internal. These overproduced in with variants prion. Mapping prion-like structures these by partial proteinase K digestion showed that most cases, extensions acquired an amyloid fold, and, strikingly, was no longer present substantially altered its location. addition five N-terminus often resulted instability loss when respective genes used replace chromosomal SUP35. prions Mot3, Swi1, Lsb2, candidate Asm4, Nsp1, Cbk1, Cpp1, based on scrambled PFRs mapped. mapping QN-rich sequence predisposes to, but does not guarantee, formation it near terminus always include actual terminus, as cases Rnq1.

Язык: Английский

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Elucidating the nanoscopic organization and dynamics of the nuclear pore complex

Nucleus, Год журнала: 2025, Номер 16(1)

Опубликована: Июнь 4, 2025

Due to its pivotal role as a regulator of nucleocytoplasmic transport, the structure and dynamic gating mechanism nuclear pore complex (NPC) is subject immense interest. Here, we report key recent advancements discussed at Selective Transport Control in Biological Biomimetic Nanopores meeting (Monte Verità, Switzerland, 2024) that gathered NPC experts from range disciplines. Novel insights were reported cutting-edge super-resolution techniques enable direct interrogation NPC's central transporter; computational models unravel mechanisms selective barrier; synthetic mimics valuable vitro for delineating permeability transport dynamics. Altogether, three major highlighted: (i) presence dynamically organised pathways within NPC, (ii) receptors enrich reinforce barrier, (iii) ability DNA origami nanostructures mimic aspects with unprecedented precision. Overall, marked convergence our understanding function by unraveling nanoscale.

Язык: Английский

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Imaging-Based Quantitative Assessment of Biomolecular Condensates in vitro and in Cells

Journal of Biological Chemistry, Год журнала: 2024, Номер 301(2), С. 108130 - 108130

Опубликована: Дек. 24, 2024

The formation of biomolecular condensates contributes to intracellular compartmentalization and plays an important role in many cellular processes. characterization is however challenging, requiring advanced biophysical or biochemical methods that are often less suitable for vivo studies. A particular need easily accessible yet thorough enable the across different experimental systems thus remains. To address this, we present PhaseMetrics, a semi-automated FIJI-based image analysis pipeline tailored quantifying particle properties from microscopy data. Tested using FG-domain yeast nucleoporin Nup100, PhaseMetrics accurately assesses diverse setups, including particles formed vitro chemically defined buffers Xenopus egg extracts systems. Comparing results with assays, conclude reliably detects changes induced by various conditions, presence polyethylene glycol, 1,6-hexanediol, salt gradient, as well activity molecular chaperone DNAJB6b protein disaggregase Hsp104. Given flexibility its parameters, should also apply other condensate-forming systems, show application detecting TDP-43 particles. By enabling accurate representation variability within population detection subtle at single-condensate level, method complements conventional assays. Combined, accessible, customizable enables imaging-based quantitative assessment cells, providing valuable addition current toolbox.

Язык: Английский

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