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Data accompanying the manuscript Lysine deserts and cullin-RING ligase receptors: Navigating untrodden paths in proteostasis

Python 3.9 Project Status: Active - The project has reached a stable, usable state and is being actively developed. DOI

License: CC BY 4.0

Overview

This repository contains codes and auxiliary data to article "Lysine-deficient proteome can be regulated through non-canonical ubiquitination and ubiquitin-independent proteasomal degradation" by Szulc et al., 2023.

What is a lysine desert and why is it important?

Lysine desert is a continuous lysine-less region of a protein. Such lysine deserts have been shown to counteract the ubiquitin-dependent turnover of equipped proteins. Understanding the role of such regions in protein functioning and degradation can shed new light on the regulation of the ubiquitin-proteasome system and play role in the development of targeted protein degradation therapies, as VHL, a crucial E3 ligase in proteolysis targeting chimeras (PROTACs) development, has an extensive lysine deserts, which elongated in the course of evolution.

Installation

Recommended usage of the jupyter notebooks deposited in this repository is in a conda environment.

Conda environment

  1. Install conda

    Please refer to the conda manual and install the conda version with Python 3.x according to your operating system.

  2. Clone the repository

    git clone https://github.com/n-szulc/fingernat.git

  3. Create conda environment

    conda env create -f /environment.yml

About the repository

Architecture

There are four main directories with codes required for performing analyses described in Szulc et al., 2013, namely Proteomes_analysis, OGs_analysis, Human_proteome_detailed_analysis, and Structral_lysine_deserts_search.

Each of the abovementioned directories contains two jupyter notebooks: Download_data.ipynb and Pipeline.ipynb. Download_data.ipynb is required to run prior Pipeline.ipynb as it allows to download data for the analyses.

All the notebooks are extensively documented with all the analyses' steps described.

Order of computational analyses

Codes from Proteomes_analysis and OGs_analysis may be run independently from other analyses.

The order for performing analyses from Human_proteome_detailed_analysis and Structural_lysine_deserts_search is as follows:

  1. Proteomes_analysis/Download_data.ipynb
  2. Structural_lysine_deserts_search/Download_data.ipynb
  3. Human_proteome_detailed_analysis/Download_data
  4. Human_proteome_detailed_analysis/Pipeline.ipynb
  5. Structural_lysine_deserts_search/Pipeline.ipynb

Supplementary tables

All supplementary tables generated during this study are deposited in subdirectories of appropriate analyses and accompanied by README files with description of their content and each column.

Experimental data

The Experimental_data directory contains raw luminescence and fluorescence measurements from the cycloheximide chase and NanoBRET ubiquitination assays.

Feedback, issues, and questions

We welcome any feedback, please send an email to Natalia Szulc

How to cite

If you used codes or datasets from this repository, please cite:

Lysine deserts and cullin-RING ligase receptors: Navigating untrodden paths in proteostasis
Natalia A. Szulc, Małgorzata Piechota, Lilla Biriczová, Pankaj Thapa, Wojciech Pokrzywa

iScience

doi: 10.1016/j.isci.2023.108344

License

This repository is licensed under the CC BY 4.0 license.

Funding

This research was supported by the National Science Centre, Poland (grant PRELUDIUM number 2021/41/N/NZ1/03473 to Natalia A. Szulc and grant SONATA-BIS number 2021/42/E/NZ1/00190 to Wojciech Pokrzywa).