Communications Biology

Journal: Communications Biology

Abbreviation

Commun Biol

Publisher

Nature

ISSN

2399-3642

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Publications 1 - 10 of 84

The main protease (Mᵖʳᵒ) from SARS-CoV-2 triggers plasma clotting in vitro by activating coagulation factors VII and FXII
Pagotto, Anna; Uliana, Federico; Cavedon, Elena; et al. (2025)
Communications Biology
Although the connection between COVID-19 and coagulopathy has been clear since the beginning of SARS-CoV-2 pandemic, the underlying molecular mechanisms remain elusive. Available data support that the hyper-coagulant state is sustained by systemic inflammation. Here we show that the SARS-CoV-2 main protease (Mᵖʳᵒ) can play a direct role in the activation of coagulation. Adding Mᵖʳᵒ to human plasma increased clotting probability by 3-fold. Enzymatic assays and degradomics analysis indicate that Mᵖʳᵒ cleaves and activates coagulation factors VII and XII. This activity is compatible with an extended secondary specificity of Mᵖʳᵒ for R↓X that diverge from its well-established preference for LQ↓X. This finding is supported by HDX-MS characterization of the Mᵖʳᵒ complex with an Arg-containing inhibitor, as well as the proteolytic cleavage of the peptide FTRLR↓SLEN by Mᵖʳᵒ. Overall, integrating biochemical, proteomics and structural biology experiments, we unveil a novel mechanism linking SARS-CoV-2 infection to thrombotic complications in COVID-19.
Quantitative proteome of bacterial periplasmic predation by Bdellovibrio bacteriovorus reveals a prey-lytic protease
Lai , Ting F.; Jankov , Denis; Grossmann , Jonas; et al. (2025)
Communications Biology
The rise of antimicrobial resistant pathogens calls for novel ways to kill and damage bacteria. A rich source for bacterial cell-damaging proteins is the periplasmic predatory bacterium Bdellovibrio bacteriovorus, which invades, kills and subsequently exits the prey cell. An increased understanding of predatory protein function can be achieved by analyzing their relative abundance at key stages of predation. We present the first quantitative proteome covering the complete predatory life cycle of B. bacteriovorus killing Escherichia coli, quantifying 2195 predator proteins. Protein clustering reveals nine distinct clusters sharing similar expression patterns. Notably, the protease Bd2269 is highly abundant during the prey exit phase. Gene knockout and heterologous expression experiments reveal that Bd2269 is involved in the prey exit process and lyses E. coli from within. Our quantitative predator proteome is a valuable resource to study specific stages of the predatory life cycle, contributing to advancing the search for novel antimicrobial enzymes.
Leaf-damaging behavior by queens is widespread among bumblebee species
Flury, Priska; Stade, Sofie; De Moraes, Consuelo M.; et al. (2025)
Communications Biology
Phenological mismatches and resource limitations resulting from ongoing environmental change can have severe impacts on pollinator fitness. Recent findings show that bumblebee workers respond to pollen scarcity by damaging plant leaves in ways that can accelerate flowering, suggesting a mechanism by which direct information transfer from bees to plants might influence the timing of flower production. However, the ecological and adaptive significance of this interaction remains uncertain. Here we report that mated and unmated queens of Bombus terrestris also damage leaves, with similar effects on flowering. Furthermore, we document leaf damage by wild-caught queens from 12 species, spanning seven subgenera, indicating damaging behavior is widespread among Bombus species. Leaf damage by bumblebee queens may have particular relevance in the context of colony founding and early development, where the timely availability of local floral resources can be critical for colony success and fitness.
Eco-evolutionary model on spatial graphs reveals how habitat structure affects phenotypic differentiation
Boussange, Victor; Pellissier, Loïc (2022)
Communications Biology
Differentiation mechanisms are influenced by the properties of the landscape over which individuals interact, disperse and evolve. Here, we investigate how habitat connectivity and habitat heterogeneity affect phenotypic differentiation by formulating a stochastic eco-evolutionary model where individuals are structured over a spatial graph. We combine analytical insights into the eco-evolutionary dynamics with numerical simulations to understand how the graph topology and the spatial distribution of habitat types affect differentiation. We show that not only low connectivity but also heterogeneity in connectivity promotes neutral differentiation, due to increased competition in highly connected vertices. Habitat assortativity, a measure of habitat spatial auto-correlation in graphs, additionally drives differentiation under habitat-dependent selection. While assortative graphs systematically amplify adaptive differentiation, they can foster or depress neutral differentiation depending on the migration regime. By formalising the eco-evolutionary and spatial dynamics of biological populations on graphs, our study establishes fundamental links between landscape features and phenotypic differentiation.
Mycorrhizal feedbacks influence global forest structure and diversity
Delavaux, Camille S.; LaManna, Joseph A.; Myers, Jonathan A.; et al. (2023)
Communications Biology
One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure.
α-Synuclein fibril and synaptic vesicle interactions lead to vesicle destruction and increased lipid-associated fibril uptake into iPSC-derived neurons
Stephens, Amberley D.; Fernandez Villegas, Ana; Chung, Chyi Wei; et al. (2023)
Communications Biology
Monomeric alpha-synuclein (aSyn) is a well characterised protein that importantly binds to lipids. aSyn monomers assemble into amyloid fibrils which are localised to lipids and organelles in insoluble structures found in Parkinson's disease patient's brains. Previous work to address pathological aSyn-lipid interactions has focused on using synthetic lipid membranes, which lack the complexity of physiological lipid membranes. Here, we use physiological membranes in the form of synaptic vesicles (SV) isolated from rodent brain to demonstrate that lipid-associated aSyn fibrils are more easily taken up into iPSC-derived cortical i3Neurons. Lipid-associated aSyn fibril characterisation reveals that SV lipids are an integrated part of the fibrils and while their fibril morphology differs from aSyn fibrils alone, the core fibril structure remains the same, suggesting the lipids lead to the increase in fibril uptake. Furthermore, SV enhance the aggregation rate of aSyn, yet increasing the SV:aSyn ratio causes a reduction in aggregation propensity. We finally show that aSyn fibrils disintegrate SV, whereas aSyn monomers cause clustering of SV using small angle neutron scattering and high-resolution imaging. Disease burden on neurons may be impacted by an increased uptake of lipid-associated aSyn which could enhance stress and pathology, which in turn may have fatal consequences for neurons.
The counterion–retinylidene Schiff base interaction of an invertebrate rhodopsin rearranges upon light activation
Nagata, Takashi; Koyanagi, Mitsumasa; Tsukamoto, Hisao; et al. (2019)
Communications Biology
Animals sense light using photosensitive proteins—rhodopsins—containing a chromophore—retinal—that intrinsically absorbs in the ultraviolet. Visible light-sensitivity depends primarily on protonation of the retinylidene Schiff base (SB), which requires a negatively-charged amino acid residue—counterion—for stabilization. Little is known about how the most common counterion among varied rhodopsins, Glu181, functions. Here, we demonstrate that in a spider visual rhodopsin, orthologue of mammal melanopsins relevant to circadian rhythms, the Glu181 counterion functions likely by forming a hydrogen-bonding network, where Ser186 is a key mediator of the Glu181–SB interaction. We also suggest that upon light activation, the Glu181–SB interaction rearranges while Ser186 changes its contribution. This is in contrast to how the counterion of vertebrate visual rhodopsins, Glu113, functions, which forms a salt bridge with the SB. Our results shed light on the molecular mechanisms of visible light-sensitivity relevant to invertebrate vision and vertebrate non-visual photoreception.
The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function
Oftedal, Bergithe E.; Maio, Stefano; Handel, Adam E.; et al. (2021)
Communications Biology
T cells rely for their development and function on the correct folding and turnover of proteins generated in response to a broad range of molecular cues. In the absence of the eukaryotic type II chaperonin complex, CCT, T cell activation induced changes in the proteome are compromised including the formation of nuclear actin filaments and the formation of a normal cell stress response. Consequently, thymocyte maturation and selection, and T cell homeostatic maintenance and receptor-mediated activation are severely impaired. In the absence of CCT-controlled protein folding, Th2 polarization diverges from normal differentiation with paradoxical continued IFN-γ expression. As a result, CCT-deficient T cells fail to generate an efficient immune protection against helminths as they are unable to sustain a coordinated recruitment of the innate and adaptive immune systems. These findings thus demonstrate that normal T cell biology is critically dependent on CCT-controlled proteostasis and that its absence is incompatible with protective immunity.
Metallo-supramolecular branched polymer protects particles from air-water interface in single-particle cryo-electron microscopy
Xu, Yixin; Qin, Yuqi; Wang, Lang; et al. (2024)
Communications Biology
Recent technological breakthroughs in single-particle cryo-electron microscopy (cryo-EM) enable rapid atomic structure determination of biological macromolecules. A major bottleneck in the current single particle cryo-EM pipeline is the preparation of good quality frozen cryo-EM grids, which is mostly a trial-and-error process. Among many issues, preferred particle orientation and sample damage by air–water interface (AWI) are common practical problems. Here we report a method of applying metallo-supramolecular branched polymer (MSBP) in the cryo-sample preparation for high-resolution single-particle cryo-EM. Our data shows that MSBP keeps a majority of particles away from air–water interface and mitigates preferred orientation as verified by the analyses of apoferritin, hemagglutinin) trimer and various sample proteins. The use of MSBP is a simple method to improve particle distribution for high-resolution structure determination in single-particle cryo-EM.
GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers
Bianco, Gaia; Coto-Llerena, Mairene; Gallon, John; et al. (2022)
Communications Biology
Synthetic lethal interactions, where the simultaneous but not individual inactivation of two genes is lethal to the cell, have been successfully exploited to treat cancer. GATA3 is frequently mutated in estrogen receptor (ER)-positive breast cancers and its deficiency defines a subset of patients with poor response to hormonal therapy and poor prognosis. However, GATA3 is not yet targetable. Here we show that GATA3 and MDM2 are synthetically lethal in ER-positive breast cancer. Depletion and pharmacological inhibition of MDM2 significantly impaired tumor growth in GATA3-deficient models in vitro, in vivo and in patient-derived organoids/xenograft (PDOs/PDX) harboring GATA3 somatic mutations. The synthetic lethality requires p53 and acts via the PI3K/Akt/mTOR pathway. Our results present MDM2 as a therapeutic target in the substantial cohort of ER-positive, GATA3-mutant breast cancer patients. With MDM2 inhibitors widely available, our findings can be rapidly translated into clinical trials to evaluate in-patient efficacy.

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Journal: Communications Biology

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