DOI: 10.5061/dryad.f7m0cfz46
title: Source data: PolyPR interaction with nuclear transport components

description: The disruption of nucleocytoplasmic transport (NCT) is an important
 mechanism in neurodegenerative diseases. In the case of C9orf72-ALS,
 trafficking of macromolecules through the nuclear pore complex (NPC) might
 get frustrated by the binding of C9orf72-translated arginine-containing
 dipeptide repeat proteins (R-DPRs) to the Kapβ family of nuclear transport
 receptors. Beside Kapβs, several other types of transport components have
 been linked to NCT impairments in R-DPRs expressed cells, but the
 molecular origin of these observations has not been clarified. Here, we
 adopt a coarse-grained molecular dynamics model at amino-acid resolution
 to study the direct interaction between polyPR, the most toxic DPR, and
 various nuclear transport components to elucidate the binding mechanisms
 and provide a complete picture of potential polyPR-mediated NCT defects.
 We found polyPR to directly bind to several isoforms of the Impα family,
 CAS (the specific exporter of Impα) and RanGAP. We observe no binding
 between polyPR and Ran. Longer polyPRs at lower salt concentrations also
 make contact with RanGEF and NTF2. Analyzing the polyPR contact sites on
 the transport components reveals that polyPR potentially interferes with
 RanGTP/RanGDP binding, with nuclear localization signal (NLS)-containing
 cargoes (cargo-NLS) binding to Impα, with cargo-NLS release from Impα, and
 with Impα export from the nucleus. The abundance of polyPR binding sites
 on multiple transport components combined with the inherent polyPR length
 dependence makes direct polyPR interference of NCT a potential mechanistic
 pathway of C9orf72 toxicity. The uploaded dataset provides details on the
 interactions between polyPR of varying lengths and different transport
 components, along with contact probabilities for individual residues.
 Refer to the README file for further information.
description: # Source data: PolyPR interaction with nuclear transport components
 [https://doi.org/10.5061/dryad.f7m0cfz46](https://doi.org/10.5061/dryad.f7m0cfz46) The dataset includes source data files used to generate all figures in the manuscript titled "C9orf72 polyPR directly binds to various nuclear transport components" [https://doi.org/10.7554/eLife.89694.2](https://doi.org/10.7554/eLife.89694.2). The Excel files and sheet titles follow the same naming convention used in the manuscript to maintain consistency. ## Description of the data and file structure Data for each figure is provided in Excel files, with separate sheets for each figure panel. ### Data and file overview #### figure2.xlsx: Source data for **figure 2** and **figure 2 figure supplements** in the manuscript. ##### Sheets: *NCPR: net charge per residue, M: Dipole moment, Rg: radius of gyration 1- fig2a-100mM/200mM: Normalized number of contacts between polyPR ( with 7,20, and 50 repeat units) and different transport components at Csalt=100mM/200mM. * X values are NCPR-fM/Rg for each transport component * Y values are the normalized number of contacts. 2- fig2b-100mM/200mM: Normalized number of contacts between polyPR (with 7,20, and 50 repeat units) and Kapbeta set at Csalt=100mM/200mM. * X values are NCPR for each transport component * Y values are the normalized number of contacts. 3- fig2-fig-supp-1a_left/right: The quality of fit (R^2) for different values of the dimensionless parameter f in Eq. (1) in the manuscript for the interaction of different sets of transport components with polyPR (with 7,50 repeat units) at Csalt=100/200 mM * fig2-fig-supp-1a_left: The quality of fit for this set: RanGEF,Ran,Impα5ΔN,KAP60ΔN,Impα1ΔN,Impα7ΔN,NTF2,Impα3ΔN,RanGAP * fig2-fig-supp-1a_right: The quality of fit for this set: Impβ1,TNPO1,KAP95,KAP124,TNPO3,KAP121,KAP114,XPO5,KAP120,Imp5,CRM1,CAS,CSE1 4- fig2-fig-supp-1b: The dipole moment (M) of transport components in units of e.nm 5- fig2-fig-supp-1c: The net charge per residue (NCPR) of transport components #### figure3.xlxs: Source data for **figure 3** and **figure 3 figure supplements** in the manuscript. ##### Sheets: 1- fig3_[transport_component_name] Each sheet presents the contact probability of individual residues of transport components interacting with polyPR (with 7,50 repeat units). In total, there are 11 transport components, with each sheet dedicated to one transport component's data: * transport_component_name: RanGEF,Ran,CAS,Cse1,Impα5ΔN,KAP60ΔN,Impα1ΔN,Impα7ΔN,NTF2,Impα3ΔN,RanGAP Column Descriptions: * "Residue Index": Index of residues within the protein sequence (derived from the PDB file sourced from the Protein Data Bank). * "con-prob-PR7/50": Probability (ranging from 0 to 1) of contact between each residue and polyPR (with repeat units 7,50). 2- fig3_bs_[transport_component_name] The information collected from the PiSITE webserver highlights the significant binding sites of individual transport components. For each transport component, relevant binding partners and the binding sites (residue indices) within the sequence of the transport component are reported. * The following abbreviations are used: IMA for Impα, GTP for RanGTP, GDP for RanGDP, NLS for cargo-NLS, and NP2 for NUP2. In total, there are 11 transport components, with each sheet containing data for one transport component: * transport_component_name: RanGEF,Ran,CAS,Cse1,Impα5ΔN,KAP60ΔN,Impα1ΔN,Impα7ΔN,NTF2,Impα3ΔN,RanGAP ## Sharing/Access information Links to publications that use the data: Hamidreza Jafarinia, Erik Van der Giessen, Patrick R. Onck (2024). PolyPR directly binds to various nuclear transport components. [https://doi.org/10.7554/eLife.89694.2](https://doi.org/10.7554/eLife.89694.2)