Biology subjects

Torrent Burgas, M.

Publications and source records attributed to Torrent Burgas, M..

4 recordsLinked to original sources

bioRxiv2022

The PRALINE database: Protein and Rna humAn singLe nucleotIde variaNts in condEnsates

SummaryBiological condensates are membraneless organelles with different material properties. Proteins and RNAs are the main components, but most of their interactions are still unknown. Here we introduce PRALINE, a database for the interrogation of proteins and RNAs contained in stress-granules, processing bodies, and other assemblies including droplets and amyloids. PRALINE provides information about the predicted and experimentally validated protein-protein, protein-RNA and RNA-RNA interactions. For proteins, it reports the liquid-liquid phase separation and liquid-solid phase separation propensities. For RNAs, it provides information on predicted secondary structure content. PRALINE shows detailed information on human single-nucleotide variants, their clinical significance and presence in protein and RNA binding sites, and how they can affect condensates physical properties. AvailabilityPRALINE is freely accessible on the web at http://alvinlee.bio.uniroma1.it/praline. Supplementary informationGeneral information is at http://alvinlee.bio.uniroma1.it/praline/about, where we provide a detailed description of the datasets and the tools employed in the database. Data provided in PRALINE are available at http://alvinlee.bio.uniroma1.it/praline/downloads. The tutorial is at http://alvinlee.bio.uniroma1.it/praline/tutorial.

bioinformatics↗

bioRxiv2022

Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy

Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here we show that treatment of Escherichia coli with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. Genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant with a view to eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments.

microbiology↗

bioRxiv2021

A spoonful of disorder regulates interactions within Stress Granules and Processing Bodies

Condensation, or liquid-like phase separation, is a phenomenon indispensable for the spatiotemporal regulation of molecules within the cell. Recent studies indicate that the composition and molecular organization of phase-separated organelles such as Stress Granules (SGs) and Processing Bodies (PBs) are highly variable and dynamic. A dense contact network involving both RNAs and proteins controls the formation of SGs and PBs and an intricate molecular architecture, at present poorly understood, guarantees that these assemblies sense and adapt to different stresses and environmental changes. Here, we investigated the physico-chemical properties of SGs and PBs components and studied the architecture of their interaction networks. We found that proteins and RNAs establishing the largest amount of contacts in SGs and PBs have distinct structural properties and intrinsic disorder is enriched in all protein-RNA, protein-protein and RNA-RNA interaction networks. The increase of disorder in proteins is accompanied by an enrichment in single-stranded regions of RNA binding partners. Our results suggest that SGs and PBs quickly assemble and disassemble through fuzzy-like dynamic contacts modulated by unfolded domains of their components. Research HighlightsO_LIWe systematically studied RNA-RNA, protein-protein and RNA-protein interaction networks in stress granules and processing bodies; C_LIO_LIRNAs enriched in stress granules and processing bodies are more single-stranded and form a large number of contacts with both proteins and RNAs; C_LIO_LIProteins in stress granules and processing bodies are less structured and contact larger amounts of single-stranded RNAs. C_LI

molecular biology↗

bioRxiv2019

The fitness cost and benefit of phase separated protein deposits

Phase separation of soluble proteins into insoluble deposits is associated with numerous diseases. However, protein deposits can also function as membrane-less compartments for many cellular processes. What are the fitness costs and benefits of forming such deposits in different conditions? Using a model protein that phase separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast. The environmental condition and the cellular demand for the protein function emerge as key determinants of fitness. Protein deposit formation can lead to cell-to-cell differences in free protein abundance between individuals. This results in variable manifestation of protein function and a continuous range of phenotypes in a cell population, favoring survival of some individuals in certain environments. Thus, protein deposit formation by phase separation might be a mechanism to sense protein concentration in cells and to generate phenotypic variability. The selectable phenotypic variability, previously described for prions, could be a general property of proteins that can form phase separated assemblies and may influence cell fitness.\n\nStand-first textUsing a model protein that phase separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast.\n\nO_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY\n\nBullet pointsO_LIThe presented approach identifies and quantifies different fitness effects associated with protein deposit formation due to phase separation\nC_LIO_LIThe environmental condition and the cellular demand for the protein function emerge as key determinants of fitness upon protein deposit formation\nC_LIO_LIVariability in protein deposit formation can lead to cell-to-cell differences in free protein abundance between individuals\nC_LIO_LIProtein phase separation can generate a continuous range of phenotypes in a cell population\nC_LI

systems biology↗