ArticleScientific reports2022
Molecular basis of C9orf72 poly-PR interference with the β-karyopherin family of nuclear transport receptors.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Kap-centric Nsp1-mediated nuclear transport at full amino acid resolution.Nature communications · 2025Article
- Beyond the ends: potential implications of telomeric repeat-containing RNA (TERRA) for CNS diseases.Journal of molecular cell biology · 2025Review
- Targeting GeneInternational journal of molecular sciences · 2025Review
- Selective phase separation of transcription factors is driven by orthogonal molecular grammar.Nature communications · 2025Article
- NLS-binding deficient Kapβ2 reduces neurotoxicity via selective interaction with C9orf72-ALS/FTD dipeptide repeats.Communications biology · 2025Article
- C9orf72 polyPR interaction with the nuclear pore complex.Biophysical journal · 2024Article
- The Effect of Dipeptide Repeat Proteins on FUS/TDP43-RNA Condensation in C9orf72 ALS/FTD.The journal of physical chemistry. B · 2024Article
- The nuclear import receptor Kapβ2 modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD.Communications biology · 2024Article
- Article
- Sulfated disaccharide protects membrane and DNA damages from arginine-rich dipeptide repeats in ALS.Science advances · 2024Article
- Diameter dependence of transport through nuclear pore complex mimics studied using optical nanopores.eLife · 2024Article
- Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD.Molecular neurodegeneration · 2024Review
- Interaction of theCells · 2023Article
- Phase separation of intrinsically disordered FG-Nups is driven by highly dynamic FG motifs.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleocytoplasmic transport (NCT) is affected in several neurodegenerative diseases including C9orf72-ALS. It has recently been found that arginine-containing dipeptide repeat proteins (R-DPRs), translated from C9orf72 repeat expansions, directly bind to several importins. To gain insight into how this can affect nucleocytoplasmic transport, we use coarse-grained molecular dynamics simulations to study the molecular interaction of poly-PR, the most toxic DPR, with several Kapβs (importins and exportins). We show that poly-PR-Kapβ binding depends on the net charge per residue (NCPR) of the Kapβ, salt concentration of the solvent, and poly-PR length. Poly-PR makes contact with the inner surface of most importins, which strongly interferes with Kapβ binding to cargo-NLS, IBB, and RanGTP in a poly-PR length-dependent manner. Longer poly-PRs at higher concentrations are also able to make contact with the outer surface of importins that contain several binding sites to FG-Nups. We also show that poly-PR binds to exportins, especially at lower salt concentrations, interacting with several RanGTP and FG-Nup binding sites. Overall, our results suggest that poly-PR might cause length-dependent defects in cargo loading, cargo release, Kapβ transport and Ran gradient across the nuclear envelope.
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