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The last 50 bibliographies

Yeast cell responses and survival during periodic osmotic stress are controlled by glucose availability

Author(s) : Duveau F, Cordier C, Chiron L, Le Bec M, Pouzet S, Seguin J, Llamosi A, Sorre B, Di Meglio J, Hersen P,
Journal : Elife
Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival, and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer, and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. Therefore, glucose availability regulates yeast responses to dynamic osmotic stress, showcasing the key role of metabolic fluctuations in cellular responses to dynamic stress. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions.

AlphaFold2 Predicts Whether Proteins Interact Amidst Confounding Structural Compatibility

Author(s) : Martin J,
Journal : J Chem Inf Model

RNAP II antagonizes mitotic chromatin folding and chromosome segregation by condensin.

Author(s) : Lebreton J, Colin L, Chatre E, Bernard P,
Journal : Cell Rep
Condensin shapes mitotic chromosomes by folding chromatin into loops, but whetherit does so by DNA-loop extrusion remains speculative. Although loop-extrudingcohesin is stalled by transcription, the impact of transcription on condensin,which is enriched at highly expressed genes in many species, remains unclear.Using degrons of Rpb1 or the torpedo nuclease Dhp1(XRN2) to either deplete ordisplace RNAPII on chromatin in fission yeast metaphase cells, we show thatRNAPII does not load condensin on DNA. Instead, RNAPII retains condensin in cisand hinders its ability to fold mitotic chromatin and to support chromosomesegregation, consistent with the stalling of a loop extruder. Transcriptiontermination by Dhp1 limits such a hindrance. Our results shed light on theintegrated functioning of condensin, and we argue that a tight control oftranscription underlies mitotic chromosome assembly by loop-extruding condensin.

Discriminating physiological from non-physiological interfaces in structures of protein complexes: a community-wide study

Author(s) : Schweke H, Xu Q, Tauriello G, Pantolini L, Schwede T, Cazals F, Lhéritier A, Fernandez-Recio J, Rodríguez-Lumbreras L, Schueler-Furman O, others,
Journal : Proteomics

Expulsion mechanism of the substrate-translocating subunit in ECF transporters

Author(s) : Thangaratnarajah C, Nijland M, Borges-Araújo L, Jeucken A, Rheinberger J, Marrink S, Souza P, Paulino C, Slotboom D,
Journal : Nature Communications

Transmembrane dimers of type 1 receptors sample alternate configurations: MD simulations using coarse grain Martini 3 versus AlphaFold2 Multimer

Author(s) : Sahoo A, Souza P, Meng Z, Buck M,
Journal : Structure

An implementation of the Martini coarse-grained force field in OpenMM

Author(s) : MacCallum J, Hu S, Lenz S, Souza P, Corradi V, Tieleman D,
Journal : Biophysical Journal

Mono- and Intralink Filter (Mi-Filter) To Reduce False Identifications in Cross-Linking Mass Spectrometry Data.

Author(s) : Chen X, Sailer C, Kammer K, Fürsch J, Eisele M, Sakata E, Pellarin R, Stengel F,
Journal : Anal Chem
Cross-linking mass spectrometry (XL-MS) has become an indispensable tool for theemerging field of systems structural biology over the recent years. However, theconfidence in individual protein-protein interactions (PPIs) depends on thecorrect assessment of individual inter-protein cross-links. In this article, wedescribe a mono- and intralink filter (mi-filter) that is applicable to any kindof cross-linking data and workflow. It stipulates that only proteins for which atleast one monolink or intra-protein cross-link has been identified within a givendata set are considered for an inter-protein cross-link and therefore participatein a PPI. We show that this simple and intuitive filter has a dramatic effect ondifferent types of cross-linking data ranging from individual protein complexesover medium-complexity affinity enrichments to proteome-wide cell lysates andsignificantly reduces the number of false-positive identifications forinter-protein links in all these types of XL-MS data.

Coevolution-Guided Mapping of the Type VI Secretion Membrane Complex-Baseplate Interface.

Author(s) : Vanlioğlu E, Santin Y, Filella-Merce I, Pellarin R, Cascales E,
Journal : J Mol Biol
The type VI secretion system (T6SS) is a multiprotein weapon evolved byGram-negative bacteria to deliver effectors into eukaryotic cells or bacterialrivals. The T6SS uses a contractile mechanism to propel an effector-loaded needleinto its target. The contractile tail is built on an assembly platform, thebaseplate, which is anchored to a membrane complex. Baseplate-membrane complexinteractions are mainly mediated by contacts between the C-terminal domain of theTssK baseplate component and the cytoplasmic domain of the TssL inner membraneprotein. Currently, the structural details of this interaction are unknown due tothe marginal stability of the TssK-TssL complex. Here we conducted a mutagenesisstudy based on putative TssK-TssL contact pairs identified by co-evolutionanalyses. We then evaluated the impact of these mutations on T6SS activity,TssK-TssL interaction and sheath assembly and dynamics in enteroaggregativeEscherichia coli. Finally, we probed the TssK-TssL interface by disulfidecross-linking, allowing to propose a model for the baseplate-membrane complexinterface.

Acinetobacter type VI secretion system comprises a non-canonical membrane complex.

Author(s) : Kandolo O, Cherrak Y, Filella-Merce I, Le Guenno H, Kosta A, Espinosa L, Santucci P, Verthuy C, Lebrun R, Nilges M, Pellarin R, Durand E,
Journal : PLoS Pathog
A. baumannii can rapidly acquire new resistance mechanisms and persist on abioticsurface, enabling the colonization of asymptomatic human host. In Acinetobacterthe type VI secretion system (T6SS) is involved in twitching, surface motilityand is used for interbacterial competition allowing the bacteria to uptake DNA.A. baumannii possesses a T6SS that has been well studied for its regulation andspecific activity, but little is known concerning its assembly and architecture.The T6SS nanomachine is built from three architectural sub-complexes. Unlike thebaseplate (BP) and the tail-tube complex (TTC), which are inherited frombacteriophages, the membrane complex (MC) originates from bacteria. The MC is themost external part of the T6SS and, as such, is subjected to evolution andadaptation. One unanswered question on the MC is how such a gigantesque molecularedifice is inserted and crosses the bacterial cell envelope. The A. baumannii MClacks an essential component, the TssJ lipoprotein, which anchors the MC to theouter membrane. In this work, we studied how A. baumannii compensates the absenceof a TssJ. We have characterized for the first time the A. baumannii's specificT6SS MC, its unique characteristic, its membrane localization, and assemblydynamics. We also defined its composition, demonstrating that its biogenesisemploys three Acinetobacter-specific envelope-associated proteins that define anintricate network leading to the assembly of a five-proteins membranesuper-complex. Our data suggest that A. baumannii has divided the function ofTssJ by (1) co-opting a new protein TsmK that stabilizes the MC and by (2)evolving a new domain in TssM for homo-oligomerization, a prerequisite to buildthe T6SS channel. We believe that the atypical species-specific features wereport in this study will have profound implication in our understanding of theassembly and evolutionary diversity of different T6SSs, that warrants futureinvestigation.

Assembly of a unique membrane complex in type VI secretion systems of Bacteroidota.

Author(s) : Bongiovanni T, Latario C, Le Cras Y, Trus E, Robitaille S, Swartz K, Schmidtke D, Vincent M, Kosta A, Orth J, Stengel F, Pellarin R, Rocha E, Ross B, Durand E,
Journal : Nat Commun
The type VI secretion system (T6SS) of Gram-negative bacteria inhibits competitorcells through contact-dependent translocation of toxic effector proteins. InProteobacteria, the T6SS is anchored to the cell envelope through amegadalton-sized membrane complex (MC). However, the genomes of Bacteroidota withT6SSs appear to lack genes encoding homologs of canonical MC components. Here, weidentify five genes in Bacteroides fragilis (tssNQOPR) that are essential forT6SS function and encode a Bacteroidota-specific MC. We purify this complex,reveal its dimensions using electron microscopy, and identify a protein-proteininteraction network underlying the assembly of the MC including the stoichiometryof the five TssNQOPR components. Protein TssN mediates the connection between theBacteroidota MC and the conserved baseplate. Although MC gene content andorganization varies across the phylum Bacteroidota, no MC homologs are detectedoutside of T6SS loci, suggesting ancient co-option and functional convergencewith the non-homologous MC of Pseudomonadota.

Carm1-arginine methylation of the transcription factor C/EBPα regulates transdifferentiation velocity

Author(s) : Torcal Garcia G, Kowenz-Leutz E, Tian T, Klonizakis A, Lerner J, De Andres-Aguayo L, Sapozhnikova V, Berenguer C, Carmona M, Casadesus M, Bulteau R, Francesconi M, Peiro S, Mertins P, Zaret K, Leutz A, Graf T,
Journal : eLife
Here, we describe how the speed of C/EBPα-induced B cell to macrophage transdifferentiation (BMT) can be regulated, using both mouse and human models. The identification of a mutant of C/EBPα (C/EBPαR35A) that greatly accelerates BMT helped to illuminate the mechanism. Thus, incoming C/EBPα binds to PU.1, an obligate partner expressed in B cells, leading to the release of PU.1 from B cell enhancers, chromatin closing and silencing of the B cell program. Released PU.1 redistributes to macrophage enhancers newly occupied by C/EBPα, causing chromatin opening and activation of macrophage genes. All these steps are accelerated by C/EBPαR35A, initiated by its increased affinity for PU.1. Wild-type C/EBPα is methylated by Carm1 at arginine 35 and the enzyme’s perturbations modulate BMT velocity as predicted from the observations with the mutant. Increasing the proportion of unmethylated C/EBPα in granulocyte/macrophage progenitors by inhibiting Carm1 biases the cell’s differentiation toward macrophages, suggesting that cell fate decision velocity and lineage directionality are closely linked processes.

Mechanism of homology search expansion during recombinational DNA break repair

Author(s) : Dumont A, Mendiboure N, Savocco J, Anani L, Moreau P, Thierry A, Modolo L, Jost D, Piazza A,
Journal : BioRxiv
Homology search catalyzed by a RecA/Rad51 nucleoprotein filament (NPF) is a central step of DNA double-strand break (DSB) repair by homologous recombination. How it operates in cells remains elusive. Here we developed a Hi-C-based methodology to map single-stranded DNA (ssDNA) contacts genome-wide in S. cerevisiae, which revealed two main homology search phases. Initial search conducted by short NPFs is confined in cis by cohesin-mediated chromatin loop folding. Progressive growth of stiff NPFs enables exploration of distant genomic sites. Long-range resection by Exo1 drives this transition from local to genome-wide search by providing ssDNA substrates for assembly of extensive NPFs. DSB end-tethering promotes coordinated homology search by NPFs formed on the two DSB ends. Finally, an autonomous genetic element on chromosome III engages the NPF and stimulates homology search in its vicinity. This work reveals the mechanism of the progressive and uneven expansion of homology search orchestrated by chromatin organizers, long-range resection, end-tethering, specialized genetic elements, and that exploits the stiff NPF structure conferred by Rad51 oligomerization.

Topological Constraints and Finite-Size Effects in Quantitative Polymer Models of Chromatin Organization

Author(s) : Abdulla A, Tortora M, Vaillant C, Jost D,
Journal : Macromolecules

Transcription induces context-dependent remodeling of chromatin architecture during differentiation.

Author(s) : Chahar S, Ben Zouari Y, Salari H, Kobi D, Maroquenne M, Erb C, Molitor A, Mossler A, Karasu N, Jost D, Sexton T,
Journal : PLoS Biol
Metazoan chromosomes are organized into discrete spatial domains (TADs), believedto contribute to the regulation of transcriptional programs. Despite extensivecorrelation between domain organization and gene activity, a direct mechanisticlink is unclear, with perturbation studies often showing little effect. To followchromatin architecture changes during development, we used Capture Hi-C tointerrogate the domains around key differentially expressed genes during mousethymocyte maturation, uncovering specific remodeling events. Notably, one TADboundary was broadened to accommodate RNA polymerase elongation past the border,and subdomains were formed around some activated genes without changes in CTCFbinding. The ectopic induction of some genes was sufficient to recapitulatedomain formation in embryonic stem cells, providing strong evidence thattranscription can directly remodel chromatin structure. These results suggestthat transcriptional processes drive complex chromosome folding patterns that canbe important in certain genomic contexts.

CGCompiler: Automated Coarse-Grained Molecule Parametrization via Noise-Resistant Mixed-Variable Optimization

Author(s) : Stroh K, Souza P, Monticelli L, Risselada H,
Journal : Journal of Chemical Theory and Computation
Coarse-grained force fields (CG FFs) such as the Martini model entail a predefined, fixed set of Lennard-Jones parameters (building blocks) to model virtually all possible nonbonded interactions between chemically relevant molecules. Owing to its universality and transferability, the building-block coarse-grained approach has gained tremendous popularity over the past decade. The parametrization of molecules can be highly complex and often involves the selection and fine-tuning of a large number of parameters (e.g., bead types and bond lengths) to optimally match multiple relevant targets simultaneously. The parametrization of a molecule within the building-block CG approach is a mixed-variable optimization problem: the nonbonded interactions are discrete variables, whereas the bonded interactions are continuous variables. Here, we pioneer the utility of mixed-variable particle swarm optimization in automatically parametrizing molecules within the Martini 3 coarse-grained force field by matching both structural (e.g., RDFs) as well as thermodynamic data (phase-transition temperatures). For the sake of demonstration, we parametrize the linker of the lipid sphingomyelin. The important advantage of our approach is that both bonded and nonbonded interactions are simultaneously optimized while conserving the search efficiency of vector guided particle swarm optimization (PSO) methods over other metaheuristic search methods such as genetic algorithms. In addition, we explore noise-mitigation strategies in matching the phase-transition temperatures of lipid membranes, where nucleation and concomitant hysteresis introduce a dominant noise term within the objective function. We propose that noise-resistant mixed-variable PSO methods can both improve and automate parametrization of molecules within building-block CG FFs, such as Martini.

Histone removal in sperm protects paternal chromosomes from premature division at fertilization

Author(s) : Dubruille R, Herbette M, Revel M, Horard B, Chang C, Loppin B,
Journal : Science
The global replacement of histones with protamines in sperm chromatin is widespread in animals, including insects, but its actual function remains enigmatic. We show that in the Drosophila paternal effect mutant paternal loss ( pal ), sperm chromatin retains germline histones H3 and H4 genome wide without impairing sperm viability. However, after fertilization, pal sperm chromosomes are targeted by the egg chromosomal passenger complex and engage into a catastrophic premature division in synchrony with female meiosis II. We show that pal encodes a rapidly evolving transition protein specifically required for the eviction of (H3-H4) 2 tetramers from spermatid DNA after the removal of H2A-H2B dimers. Our study thus reveals an unsuspected role of histone eviction from insect sperm chromatin: safeguarding the integrity of the male pronucleus during female meiosis. , Editor’s summary Ultracompaction of sperm DNA in many species is often associated with genome-wide replacement of histones with protamines, but the actual role of this radical change in chromatin organization remains largely enigmatic. Looking at a multidecade-old Drosophila mutant, Dubruille et al . found that histones were massively retained in sperm without affecting its ability to fertilize (see the Perspective by Levine). However, at fertilization, male chromosomes were aberrantly recognized by maternal factors that control female meiotic progression, leading to a deleterious premature division and early loss of male chromosomes. This work highlights the role of sperm chromatin in protecting male chromosomes in the egg. —Di Jiang , Histone retention in Drosophila sperm chromatin jeopardizes paternal chromosome integrity during female meiosis.

Condensin positioning at telomeres by shelterin proteins drives sister-telomere disjunction in anaphase

Author(s) : Colin L, Reyes C, Berthezene J, Maestroni L, Modolo L, Toselli E, Chanard N, Schaak S, Cuvier O, Gachet Y, Coulon S, Bernard P, Tournier S,
Journal : eLife
The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome-remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosome arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.

SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans.

Author(s) : Robert V, Caron M, Gely L, Adrait A, Pakulska V, Couté Y, Chevalier M, Riedel C, Bedet C, Palladino F,
Journal : Development
The SIN3 transcriptional coregulator influences gene expression through multipleinteractions that include histone deacetylases (HDACs). Haploinsufficiency andmutations in SIN3 are the underlying cause of Witteveen-Kolk syndrome and relatedintellectual disability (ID)/autism syndromes, emphasizing its key role indevelopment. However, little is known about the diversity of its interactions andfunctions in developmental processes. Here we show that loss of SIN-3, the singleSIN3 homologue in Caenorhabditis elegans, results in maternal effect sterilityassociated with deregulation of the germline transcriptome, including desilencingof X-linked genes. We identify at least two distinct SIN3 complexes containingspecific HDACs, and show that they differentially contribute to fertility. Singlecell smFISH reveals that in sin-3 mutants, the X chromosome becomes re-expressedprematurely and in a stochastic manner in individual germ cells, suggesting arole for SIN-3 in its silencing. Furthermore, we identify histone residues whoseacetylation increases in the absence of SIN3. Together, this work provides apowerful framework for the in vivo study of SIN3 and associated proteins.

Programmed DNA elimination in Mesorhabditis nematodes

Author(s) : Rey C, Launay C, Wenger E, Delattre M,
Journal : Curr Biol