BFVD—a large repository of predicted viral protein structures

Nucleic Acids Research, Год журнала: 2024, Номер 53(D1), С. D340 - D347

Опубликована: Ноя. 22, 2024

Abstract The AlphaFold Protein Structure Database (AFDB) is the largest repository of accurately predicted structures with taxonomic labels. Despite providing predictions for over 214 million UniProt entries, AFDB does not cover viral sequences, severely limiting their study. To address this, we created Big Fantastic Virus (BFVD), a 351 242 protein by applying ColabFold to sequence representatives UniRef30 clusters. By utilizing homology searches across two petabases assembled sequencing data, improved 36% these structure beyond ColabFold’s initial results. BFVD holds unique repertoire as 62% its entries show no or low structural similarity existing repositories. We demonstrate how substantial fraction bacteriophage proteins, which remained unannotated based on can be matched similar from BFVD. In that, par AFDB, while holding nearly three orders magnitude fewer structures. an important virus-specific expansion repositories, offering new opportunities advance research. freely downloaded at bfvd.steineggerlab.workers.dev and queried using Foldseek labels bfvd.foldseek.com.

Язык: Английский

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BFVD - a large repository of predicted viral protein structures

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

The AlphaFold Protein Structure Database (AFDB) is the largest repository of accurately predicted structures with taxonomic labels. Despite providing predictions for over 214 million UniProt entries, AFDB does not cover viral sequences, severely limiting their study. To bridge this gap, we created Big Fantastic Virus (BFVD), a 351,242 protein by applying ColabFold to sequence representatives UniRef30 clusters. BFVD holds unique repertoire as 63% its entries show no or low structural similarity existing repositories. We demonstrate how substantially enhances fraction annotated bacteriophage proteins compared sequence-based annotation using Bakta. In that, on par AFDB, while holding nearly three orders magnitude fewer structures. an important virus-specific expansion structure repositories, offering new opportunities advance research. freely available at https://bfvd.steineggerlab.workers.dev/

Язык: Английский

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Molecular characterization of two newly recognized lysozymes of the protist Dictyostelium discoideum

Developmental & Comparative Immunology, Год журнала: 2025, Номер 164, С. 105334 - 105334

Опубликована: Фев. 3, 2025

Язык: Английский

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A Puccinia striiformis f. sp. tritici Effector with DPBB Domain Suppresses Wheat Defense

Plants, Год журнала: 2025, Номер 14(3), С. 435 - 435

Опубликована: Фев. 2, 2025

Wheat (Triticum aestivum L.) is a primary crop globally. Among the numerous pathogens affecting wheat production, Puccinia striiformis f. sp. tritici (Pst) significant biotic stress agent and poses major threat to world food security by causing stripe rust or yellow disease. Understanding molecular basis of plant–pathogen interactions crucial for developing new means disease management. It well established that effector proteins play pivotal role in pathogenesis. Therefore, studying has become an important area research plant biology. Our previous work identified differentially expressed candidate secretory based on transcriptome sequencing data from susceptible (Avocet S) resistant YR10) infected with Pst. secreted proteins, PSTG_14090 contained ancient double-psi beta-barrel (DPBB) fold, which conserved rare lipoprotein A (RlpA) superfamily. This study investigated immune responses, encodes protein, here referred as Pst-DPBB, having 131 amino acids predicted signal peptide (SP) 19 at N-terminal end, DNA sequence this highly among different races. qRT-PCR analysis indicated expression levels are upregulated during early stages infection. Subcellular localization studies Nicotiana benthamiana leaves protoplasts revealed it distributed cytoplasm, nucleus, apoplast. We demonstrated Pst-DPBB negatively regulates response functioning various compartments cells. Based Co-IP structural predictions putative interaction analyses AlphaFold 3, we propose probable biological function(s). behaves papain inhibitor cysteine protease; high homology kiwellin, known interact chorismate mutase, suggesting inhibits native function host mutase involved salicylic acid synthesis. The DPBB fold also RNA, may suggest its possible regulating gene expression.

Язык: Английский

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GenomeOcean: An Efficient Genome Foundation Model Trained on Large-Scale Metagenomic Assemblies

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

ABSTRACT Genome foundation models hold transformative potential for precision medicine, drug discovery, and understanding complex biological systems. However, existing are often inefficient, constrained by suboptimal tokenization architectural design, biased toward reference genomes, limiting their representation of low-abundance, uncultured microbes in the rare biosphere. To address these challenges, we developed GenomeOcean , a 4-billion-parameter generative genome model trained on over 600 Gbp high-quality contigs derived from 220 TB metagenomic datasets collected diverse habitats across Earth’s ecosystems. A key innovation is training directly large-scale co-assemblies samples, enabling enhanced microbial species improving generalizability beyond genome-centric approaches. We implemented byte-pair encoding (BPE) strategy sequence generation, alongside optimizations, achieving up to 150× faster generation while maintaining high fidelity. excels representing generating protein-coding genes evolutionary principles. Additionally, its fine-tuned demonstrates ability discover novel biosynthetic gene clusters (BGCs) natural genomes perform zero-shot synthesis biochemically plausible, complete BGCs. sets new benchmark research, product synthetic biology, offering robust advancing fields.

Язык: Английский

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Discovery of widespread activating mutations in a compact RNA-guided endonuclease

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

TnpB is an evolutionarily diverse family of RNA-guided endonucleases associated with prokaryotic transposons. Due to their small size and putative evolutionary relationship Cas12s, holds significant potential for genome editing mechanistic exploration. However, most TnpBs lack robust gene-editing activity, unbiased profiling mutational effects on activity has not been experimentally explored. Here, we mapped comprehensive sequence-function landscapes a ribonucleoprotein discovered many activating mutations in both the protein RNA. Single-position changes RNA outperform existing variants, highlighting utility systematic scaffold mutagenesis. Leveraging landscape protein, identified enhanced variants from combinatorial library mutations. These increased human cells N. benthamiana by over two-fold fifty-fold relative wild-type TnpB, respectively. In total, this study highlights unknown elements critical regulation endonuclease RNA, reveals surprising amount latent accessible through mutation.

Язык: Английский

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Metagenomic mining reveals novel viral histones in dsDNA viruses

hLife, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Structural basis for Lamassu-based antiviral immunity and its evolution from DNA repair machinery

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Bacterial immune systems exhibit remarkable diversity and modularity, as a consequence of the continuous selective pressures imposed by phage predation. Despite recent mechanistic advances, evolutionary origins many antiphage remain elusive, especially for those that encode homologs Structural Maintenance Chromosomes (SMC) superfamily, which are essential chromosome maintenance DNA repair across domains life. Here, we elucidate structural basis emergence Lamassu, bacterial system family featuring diverse effectors but core conserved SMC-like sensor. Using cryo-EM, determined structures Vibrio cholerae Lamassu complex in both apo- dsDNA-bound states, revealing unexpected stoichiometry topological architectures. We further demonstrate how specifically senses dsDNA vitro replication vivo , thereby triggering formation LmuA tetramers activate Cap4 nuclease domain. Our findings reveal evolved via exaptation Rad50-Mre11 to form compact, modular sensor viral replication, exemplifying cellular machinery can be co-opted novel functions.

Язык: Английский

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Conserved effectors underpin the virulence of liverwort-isolated Pseudomonas in divergent plants

Current Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Plant pathogenic Pseudomonas species naturally antagonize a diverse range of flowering plants. While emerging research demonstrates that isolates belonging to the P. syringae complex colonize hosts, extent which these bacteria infect non-flowering plants like model liverwort Marchantia polymorpha remains unclear. Here, we identify natural associations between viridiflava and polymorpha. isolated from diseased liverworts in wild successfully re-infected M. under pure culture conditions, producing high planta bacterial densities causing prominent tissue maceration. Comparative genomic analysis Marchantia-associated identified core virulence machinery type III secretion system (T3SS) conserved effectors (AvrE HopM1) were essential for infection. Disease assays performed Nicotiana benthamiana further confirmed liverwort-associated an effector-dependent manner. Our work highlights as effective broad host pathogen relies on factors manipulate evolutionarily divergent

Язык: Английский

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Muscle-3D: scalable multiple protein structure alignment

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 28, 2024

ABSTRACT Protein multiple alignment is an essential step in many bioinformatics analysis such as phylogenetic tree estimation, HMM construction and critical residue identification. Structure conserved between distantly-related proteins where amino acid similarity weak or undetectable, suggesting that structure-informed sequence alignments might offer advantages over constructed from sequences alone. The advent of the AI folding era has unleashed millions high-quality predicted structures, motivating development assessment scalable structure (MStA) methods. Here, we describe Muscle-3D, a new MStA algorithm combining rich representation context, Reseek “mega-alphabet”, with state-of-the art techniques Muscle5 including posterior decoding pair-HMM, consistency transformation, iterative refinement ensemble construction. We show Muscle-3D readily scales to thousands structures. Comparative validation on several benchmark datasets using different quality metrics shows be among higher-scoring methods, but find rankings disagree despite low P-values according Wilcoxon rank-sum test. suggest these conflicts arise inherently fuzzy nature structural alignment, argue universal standard accuracy not possible principle. contact map profiles for visualizing variation inter-residue distances, introduce novel measure local conformation similarity, LDDT-muw. software available at https://github.com/rcedgar/muscle .

Язык: Английский

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