Gabriele Orlando1,2, Daniele Raimondi3, Francesco Tabaro4, Francesco Codicè5, Yves Moreau3, Wim F Vranken1,2,6. 1. Interuniversity Institute of Bioinformatics in Brussels, ULB-VUB, 1050 Brussels, Belgium. 2. Structural Biology Brussels, Department of Bioengineering Sciences, Vrije Universiteit Brussel, 1050 Brussels, Belgium. 3. ESAT-STADIUS, KU Leuven, Leuven 3001, Belgium. 4. Institute of Biosciences and Medical Technology, Tampere 33520, Finland. 5. Department of Computer Science and Engineering, University of Bologna, Bologna 40127, Italy. 6. Center for Structural Biology, VIB, 1050 Brussels, Belgium.
Abstract
MOTIVATION: Eukaryotic cells contain different membrane-delimited compartments, which are crucial for the biochemical reactions necessary to sustain cell life. Recent studies showed that cells can also trigger the formation of membraneless organelles composed by phase-separated proteins to respond to various stimuli. These condensates provide new ways to control the reactions and phase-separation proteins (PSPs) are thus revolutionizing how cellular organization is conceived. The small number of experimentally validated proteins, and the difficulty in discovering them, remain bottlenecks in PSPs research. RESULTS: Here we present PSPer, the first in-silico screening tool for prion-like RNA-binding PSPs. We show that it can prioritize PSPs among proteins containing similar RNA-binding domains, intrinsically disordered regions and prions. PSPer is thus suitable to screen proteomes, identifying the most likely PSPs for further experimental investigation. Moreover, its predictions are fully interpretable in the sense that it assigns specific functional regions to the predicted proteins, providing valuable information for experimental investigation of targeted mutations on these regions. Finally, we show that it can estimate the ability of artificially designed proteins to form condensates (r=-0.87), thus providing an in-silico screening tool for protein design experiments. AVAILABILITY AND IMPLEMENTATION: PSPer is available at bio2byte.com/psp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: Eukaryotic cells contain different membrane-delimited compartments, which are crucial for the biochemical reactions necessary to sustain cell life. Recent studies showed that cells can also trigger the formation of membraneless organelles composed by phase-separated proteins to respond to various stimuli. These condensates provide new ways to control the reactions and phase-separation proteins (PSPs) are thus revolutionizing how cellular organization is conceived. The small number of experimentally validated proteins, and the difficulty in discovering them, remain bottlenecks in PSPs research. RESULTS: Here we present PSPer, the first in-silico screening tool for prion-like RNA-binding PSPs. We show that it can prioritize PSPs among proteins containing similar RNA-binding domains, intrinsically disordered regions and prions. PSPer is thus suitable to screen proteomes, identifying the most likely PSPs for further experimental investigation. Moreover, its predictions are fully interpretable in the sense that it assigns specific functional regions to the predicted proteins, providing valuable information for experimental investigation of targeted mutations on these regions. Finally, we show that it can estimate the ability of artificially designed proteins to form condensates (r=-0.87), thus providing an in-silico screening tool for protein design experiments. AVAILABILITY AND IMPLEMENTATION: PSPer is available at bio2byte.com/psp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Luciano Kagami; Joel Roca-Martínez; Jose Gavaldá-García; Pathmanaban Ramasamy; K Anton Feenstra; Wim F Vranken Journal: BMC Mol Cell Biol Date: 2021-04-23