Particle fusion of super-resolution data reveals the unit structure of Nup96 in Nuclear Pore Complex DOI Creative Commons
Wenxiu Wang, Arjen J. Jakobi, Yule Wu

и другие.

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Авг. 16, 2023

Single molecule localization microscopy offers resolution nearly down to the molecular level with specific labelling, and is thereby a promising tool for structural biology. In practice, however, actual value this field limited primarily by incomplete fluorescent labelling of structure. This missing information can be completed merging from many structurally identical particles in particle fusion approach similar cryo-EM single-particle analysis. paper, we present data analysis results fluorescently labelled Nup96 nucleoporins Nuclear Pore Complex show that occurs spatial arrangement two rings 8 units copies per unit giving total 32 pore. We use Artificial Intelligence assisted modeling Alphafold extend existing model accurately pinpoint positions labels accuracy match between better than 3 nm in-plane 5 out-of-plane.

Язык: Английский

You are who your friends are—nuclear pore proteins as components of chromatin‐binding complexes DOI Creative Commons
Maya Capelson

FEBS Letters, Год журнала: 2023, Номер 597(22), С. 2769 - 2781

Опубликована: Сен. 1, 2023

Nuclear pore complexes are large multicomponent protein that embedded in the nuclear envelope, where they mediate nucleocytoplasmic transport. In addition to supporting transport, components, termed nucleoporins (Nups), can interact with chromatin and influence genome function. A subset of Nups also localize interior bind intranuclearly, providing an opportunity investigate chromatin‐associated functions outside transport context. This review focuses on gene regulatory such intranuclear Nups, a particular emphasis their identity as components several complexes. Recent proteomic screens have identified interacting partners active repressive epigenetic machinery, architectural proteins, DNA replication complexes, insight into molecular mechanisms via which regulate expression programs. summarizes these interactions discusses potential broader framework organization.

Язык: Английский

Процитировано

9
Nanoimaging of SARS-CoV-2 viral invasion toward the nucleus and genome DOI Creative Commons
Elma Sakinatus Sajidah, Keesiang Lim, Masaharu Hazawa

и другие.

Cell Reports Physical Science, Год журнала: 2024, Номер 5(9), С. 102111 - 102111

Опубликована: Июль 24, 2024

The SARS-CoV-2 virus, responsible for the COVID-19 pandemic, has been linked to significant worldwide illness and death. Examining ultrastructure nanomechanical characteristics of viruses, from a physical standpoint, aids in categorizing their mechanical attributes, providing valuable information novel treatment approaches pinpointing susceptible regions that can guide precise medical interventions. This review presents structural virus particles, focusing on interaction with cells effects nuclear pore transit epigenetic modifications. We present latest progress utilizing high-speed atomic force microscope nanoscale observation its constituents. viruses utilize several components interact host's transport receptors nucleoporins complex influence genome modality. In this review, we also provide an updated summary how parts system these interactions change chromatin.

Язык: Английский

Процитировано

3
Nucleoporin Nsp1 surveils the phase state of FG-Nups DOI Creative Commons
Tegan A. Otto, Tessa Bergsma, Maurice Dekker

и другие.

Cell Reports, Год журнала: 2024, Номер 43(10), С. 114793 - 114793

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

3
Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis DOI Open Access
Jingjing Li, Xinyue Wang,

Laia Jordana

и другие.

Опубликована: Янв. 23, 2025

In animals, mitosis involves the breakdown of nucleus. The reassembly a nucleus after requires reformation nuclear envelope around single mass chromosomes. This process Ankle2 (also known as LEM4 in humans) which interacts with PP2A and promotes function Barrier-to-Autointegration Factor (BAF). Upon dephosphorylation, BAF dimers cross-bridge chromosomes bind lamins transmembrane proteins reassembling envelope. How functions is incompletely understood. Using combination approaches Drosophila , along structural modeling, we provide several lines evidence that suggest regulatory subunit PP2A, explaining how it dephosphorylation. addition, discovered endoplasmic reticulum protein Vap33, required for localization at during telophase. We identified interaction sites Vap33 on Ankle2. Through genetic rescue experiments, show Ankle2/PP2A essential Ankle2/Vap33 also this process. Our study sheds light molecular mechanisms post-mitotic suggests not merely source membranes process, but provides localized enzymatic activity.

Язык: Английский

Процитировано

0
Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps DOI Creative Commons

Amita Singh,

Victor Fourcassié,

Karen Cristine Gonçalves dos Santos

и другие.

Frontiers in Virology, Год журнала: 2025, Номер 5

Опубликована: Фев. 3, 2025

The novel HIV-1 drugs GS-CA1 and the recently approved lenacapavir (GS-6207) target viral structural protein capsid (CA). However, their multiple mechanisms of action have not been fully characterized. Here, we investigated effects on early stages infection, specifically steps involving nuclear envelope, in comparison to antiviral cytokine IFN-β. Mass spectrometry data indicated that envelope proteins were only modestly affected by either treatment or but combining two had a more significant impact, altering levels many including proteasomal components. induced small clear accumulation cores at pores, as seen microscopy, whereas IFN-β caused strong pores. These observations are consistent with inhibiting translocation through

Язык: Английский

Процитировано

0
Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis DOI Creative Commons
Jingjing Li, Xinyue Wang,

Laia Jordana

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Фев. 18, 2025

In animals, mitosis involves the breakdown of nucleus. The reassembly a nucleus after requires reformation nuclear envelope around single mass chromosomes. This process Ankle2 (also known as LEM4 in humans) which interacts with PP2A and promotes function Barrier-to-Autointegration Factor (BAF). Upon dephosphorylation, BAF dimers cross-bridge chromosomes bind lamins transmembrane proteins reassembling envelope. How functions is incompletely understood. Using combination approaches Drosophila , along structural modeling, we provide several lines evidence that suggest regulatory subunit PP2A, explaining how it dephosphorylation. addition, discovered endoplasmic reticulum protein Vap33, required for localization at during telophase. We identified interaction sites Vap33 on Ankle2. Through genetic rescue experiments, show Ankle2/PP2A essential Ankle2/Vap33 also this process. Our study sheds light molecular mechanisms post-mitotic suggests not merely source membranes process, but provides localized enzymatic activity.

Язык: Английский

Процитировано

0
Correlative In Situ Cryo-ET Reveals Cellular and Viral Remodeling Associated with Selective HIV-1 Core Nuclear Import DOI Creative Commons

Zhen Hou,

Y. Shen, Stanley Fronik

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Abstract Lentiviruses like HIV-1 infect non-dividing cells by traversing the nuclear pore, but studying this process has been challenging due to its scarcity and dynamic nature in infected cells. Here, we developed a robust cell-permeabilization system that recapitulates import established an integrated cryo-correlative workflow combining cryo-CLEM, cryo-FIB, cryo-ET for targeted imaging of process. These advancements enabled successful capture 1,899 cores at various stages import. Statistical structural analyses native wild-type mutant revealed depends on both capsid elasticity pore adaptability, as well factors such CPSF6. Brittle fail enter complex (NPC), while CPSF6-binding-deficient stall inside NPC, resulting impaired Intriguingly, pores function selective filters favoring smaller, tube-shaped cores. Our study opens new avenues dissecting biochemistry biology downstream events including core uncoating potentially integration, with unprecedented detail.

Язык: Английский

Процитировано

0
Homeostatic regulation of nucleoporins is a central driver of nuclear pore biogenesis DOI Creative Commons
Stephen Sakuma,

Marcela Raı́ces,

Ethan Y.S. Zhu

и другие.

Cell Reports, Год журнала: 2025, Номер unknown, С. 115468 - 115468

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
ZC3HC1 has functions distinct from TPR and is dispensable for TPR localisation to the nuclear basket DOI Creative Commons
Bethany M Bartlett, Juan Carlos Acosta, Wendy A. Bickmore

и другие.

Wellcome Open Research, Год журнала: 2025, Номер 10, С. 188 - 188

Опубликована: Апрель 11, 2025

The nuclear basket is a 'fishtrap'-like structure on the nucleoplasmic face of pore complex which has been implicated in diverse functions including RNA export, heterochromatin organisation, and mitosis. Recently, novel component basket, ZC3HC1, described. localisation ZC3HC1 to pores reported occur reciprocally with TPR, major structural basket. Using siRNA-mediated knock down, immunofluorescence sequencing we compare consequences depleting two proteins - TPR ZC3HC1. We show that human fibroblasts, although TPR-dependent, localises regardless presence demonstrate knockdown produce distinct transcriptional profiles. Our results suggest there little overlap function between these diploid fibroblasts.

Язык: Английский

Процитировано

0
Novel biallelicNUP107variants affect the nuclear pore complex and expand the clinical spectrum to include brain malformations DOI

Loisa Dana Bonde,

Laura Hecher,

Malik Alawi

и другие.

Journal of Medical Genetics, Год журнала: 2025, Номер unknown, С. jmg - 110671

Опубликована: Май 11, 2025

Biallelic variants in NUP107 cause isolated or syndromic steroid-resistant nephrotic syndrome (SRNS), characterised by proteinuria, hypoalbuminaemia and focal segmental glomerulosclerosis that progresses to end-stage renal disease. Patients with SRNS have microcephaly, developmental delay intellectual disability short stature. Simplified gyration is observed some individuals. We report on a 2-year-old girl novel biallelic variants, c.2606G>T; p.(Gly869Val) c.1576+1G>A, proteinuria severe neurodevelopmental disorder delay, early-onset seizures, sensorineural hearing loss brain structural anomalies, including simplified gyral pattern hypoplasia of the corpus callosum, pons, brainstem cerebellum. part NUP107-160 complex, which, together other proteins termed nucleoporins, forms nuclear pore complex (NPC). The NPC regulates nucleocytoplasmic transport cellular processes. In patient-derived fibroblasts, we identified aberrantly spliced mRNAs frameshift premature stop codon leading non-sense-mediated mRNA decay, reduced levels transcripts, NUP133 proteins, number. addition, an abnormal nucleolar morphology was found cells. Our functional data support conclusion underlie patient’s phenotype, thereby broadening clinical spectrum associated include development.

Язык: Английский

Процитировано

0