PLoS Genetics最新文献

{"title":"Distinct core minor pilin complexes prime specialized type IV filaments in cyanobacteria.","authors":"Nils Schuergers, Lars Wittig, Gen Enomoto, Julia Herz, Shamphavi Sivabalasarma, Katharina Ruoff, Friedel Drepper, Sonja-Verena Albers, Pitter F Huesgen, Annegret Wilde","doi":"10.1371/journal.pgen.1012337","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012337","url":null,"abstract":"<p><p>The model cyanobacterium, Synechocystis sp. PCC 6803 encodes in addition to the major pilin of the Type IV pilus filament, an extensive, partially uncharacterized repertoire of minor pilins. For those cyanobacterial minor pilins that have been characterized, their roles span a surprisingly diverse range of functions. To elucidate the roles of uncharacterized minor pilins in a systematic way, we applied structural phylogenomics across 90 genomes, classifying cyanobacterial pilins into six conserved families that form two distinct putative core priming complexes. We demonstrate that these complexes initiate the assembly of two morphologically distinct Type IV pilus filaments: short, hyper-dynamic pili for natural competence, and long, adhesive pili for motility and phototaxis. Structural analysis revealed a conserved beta-solenoid domain in PilX subunits, which we propose fulfills the capping function of PilY1 homologs. Proteomic data indicate that the minor pilin PilX2 facilitates the assembly of motility pili, which is required to maintain DnaJ3 co-chaperone levels and trigger cAMP-dependent surface sensing. These findings challenge the concept of a single multipurpose pilus, establishing that cyanobacteria utilize a shared machinery to assemble two specialized filaments, each primed by distinct core minor pilin complexes to meet the conflicting biophysical requirements of DNA uptake and surface motility.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012337"},"PeriodicalIF":3.9,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149276160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extensive mobilome heterogeneity in a widespread endosymbiont: A candidate dimeric plasmid and highly fragmented prophages in Wolbachia from Culex pipiens.","authors":"Alice Brunner, Maxime Mahout, Julien Amoros, Massilva Rahmoun, Mateo Jarry, Seth R Bordenstein, Sarah R Bordenstein, Blandine Trouche, Julie Reveillaud","doi":"10.1371/journal.pgen.1012347","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012347","url":null,"abstract":"<p><p>The obligate, intracellular bacteria Wolbachia have gained increasing interest due to their selfish modifications of host arthropod reproduction, impacts on host evolution, and utility in vector control efforts to reduce arbovirus transmission worldwide. Despite their highly reduced genomes, Wolbachia harbor a rich mobilome that includes phages, insertion sequences and plasmids in mosquito vectors. However, these repeat-rich mobile genetic elements are notoriously difficult to assemble and can generate artificial, chimeric sequences that obscure their true diversity. As a result, conventional genome sequencing and assembly approaches often fail to resolve the complexity, leaving critical gaps of knowledge on how these elements evolve, mobilize, and shape both symbiont and host genomes. To address these challenges, we established a novel Oxford Nanopore long-read sequencing strategy that avoids prior PCR amplification and leverages single-dissected, female ovaries. Using this approach, we report and characterize-directly from native long-read molecules-the first near-complete Wolbachia genome and its mobile elements from individual ovaries of the mosquito vector Culex pipiens molestus. Additional short reads from individuals of the same strain were used to assess and validate candidate mutations, particularly in repetitive regions. We report a new dimeric structure of the pWCP plasmid, suggesting the existence of multimeric plasmid forms potentially associated with active replication. We also observed extensive fragmentation of prophage WO regions despite long read sequencing, underscoring their structural complexity. Raw long read analyses recovered multiple alternative gene syntenies within WO regions, pointing to heterogeneous prophage architectures missed by the assembly and marked diversity of WO elements in Wolbachia of Culex pipiens (wPip) group strains. Taken together, our results illuminate the structural heterogeneity of the endosymbiont genome that is shaped by integrated and episomal mobile elements.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012347"},"PeriodicalIF":3.9,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149276140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auxilin in enteroendocrine cells controls intestinal homeostasis through inter-cell signaling relays.","authors":"Runqi Wang, Zhengran Li, Jing Wei, Jiajia Wang, Xiyue Liu Tao, Danjie Zhang, Ruiyan Kong, Xuejing Ren, Hang Zhao, Zhouhua Li","doi":"10.1371/journal.pgen.1012353","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012353","url":null,"abstract":"<p><p>Adult stem cells are critical for the homeostasis of residential tissue and organism fitness. Residential stem cells must constantly perceive external and internal signals and adjust their proliferation rate accordingly to avoid unlimited proliferation or premature differentiation. However, how differentiated cells affect stem cell proliferation and tissue homeostasis through cell-cell communication still remains poorly understood. Here, we unveil an unprecedented function of Auxilin (Aux) in enteroendocrine cells (EEs) by restricting intestinal stem cell (ISC) proliferation. aux depletion in all EEs leads to intestinal homeostasis disruption. The levels of Slit are dramatically reduced in aux-depleted EEs and cytokine Upd3 expression is significantly increased in some aux-depleted EEs and neighboring wild type enterocytes (ECs). Ectopic expression of slit could effectively rescue the defects observed in prosts > auxRNAi intestines. Interestingly, EGFR signaling is ectopically activated due to EGFR accumulation in aux-depleted EEs. Further inhibiting EGFR signaling completely suppresses the defects in prosts > auxRNAi intestines. Finally, EGFR signaling suppresses slit transcription by Pointed binding to slit regulatory regions. Together, these data show that Aux in EEs restrains ISCs from excessive proliferation and aberrant progeny differentiation to maintain intestinal homeostasis through inter-cell communications. Thus our study uncovers the underlying mechanism of how stem cell proliferation is properly controlled by differentiated cells through inter-cell signaling relays during tissue homeostasis and tumorigenesis.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012353"},"PeriodicalIF":3.9,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149276188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of high-grade serous ovarian cancers reveals heterogeneity and distinct immunological patterns based upon clinico-genomic status.","authors":"Jing Qian, Rania Bassiouni, Yuxin Jin, Seeta Rajpara, Monica Neuman, Varun U Khetan, Bodour Salhia, David W Craig, Joseph W Carlson, Lynda D Roman, John D Carpten","doi":"10.1371/journal.pgen.1012355","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012355","url":null,"abstract":"<p><p>High-grade serous ovarian cancer (HGSOC) is characterized by remarkable intratumoral heterogeneity and variable tissue architectures, dictating differential therapeutic responses. Although BRCA1/2 mutations correlate with improved responses to DNA-damaging agents, how BRCA genotype shapes the tumor immune microenvironment (TIME) remains incompletely understood. Here, we integrated whole exome sequencing, total RNA sequencing and spatial transcriptomics to profile a cohort of BRCA-mutated (BRCA-MT) and non-BRCA-mutated (BRCA-WT) HGSOC tumors. While bulk transcriptomics highlighted global phenotypic shifts, suggesting a more pro-inflammatory milieu in BRCA-MT tumors, spatially resolved analysis revealed how these differences manifest within specific tissue architectures. Integrated clustering revealed recurrent spatial transcriptional states across genotypes. Specifically, we identified a transcriptionally distinct immune-enriched region (IC7) characterized by low tumor purity, interferon signaling, and antigen-presentation programs. Reference-based RCTD deconvolution provided orthogonal computational support that IC7 was enriched for T/NK and dendritic cells relative to non-IC7 regions. At the patient level, the functional state of IC7 was highly BRCA-dependent: BRCA-MT tumors exhibited stronger enrichment of interferon-α/γ responses and inflammatory signaling than BRCA-WT tumors. Exploratory CellChat analysis further suggested genotype-associated differences in predicted immune-related signaling. We also identify a conserved structural interface between CAF-like region (IC3) and macrophage-rich region (IC4), accompanied by a predicted CXCL12-CXCR4 chemokine recruitment axis. Taken together, these findings support a model in which BRCA mutation status is associated with functional differences within broadly conserved spatial regions, rather than extensive reorganization of the overall spatial architecture. This spatially resolved framework identifies BRCA-associated immune transcriptional patterns in HGSOC and provides a basis for future mechanistic validation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012355"},"PeriodicalIF":3.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis of over 8,000 individuals from Hawai'i and Samoa for genetic associations to cardiometabolic phenotypes.","authors":"Bryan L Dinh, Xinran Wang, Xin Sheng, Peggy Wan, Amit Kumar Srivastava, Take Naseri, Satupa'itea Viali, Lynne Wilkens, Loïc Le Marchand, Christopher Haiman, Daniel E Weeks, Charleston W K Chiang, Jenna C Carlson","doi":"10.1371/journal.pgen.1012342","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012342","url":null,"abstract":"<p><p>Although genome-wide association studies (GWAS) now routinely reveal genetic associations and biological insights in millions of individuals, underrepresentation of global populations, such as those from Polynesia, continue to persist. These exclusions, often driven by logistical challenges and lack of data, prevent systematic identification of population-enriched associations, such as the association of the missense variant at the CREBRF locus to BMI and type 2 diabetes discovered commonly occurring in Polynesian populations due to its rarity in global populations. Armed with the recently updated TOPMed imputation panel that could benefit studies in diverse populations that previously had poorer imputation performance, we performed the first GWAS of Native Hawaiians and Samoans, the largest to date of Polynesian-ancestry populations (combined N up to 8,461) to identify population-enriched associations for 13 adiposity and cardiometabolic traits available across both cohorts: BMI, fasting glucose, fasting insulin, HDL, height, hip circumference, HOMA-IR, LDL, T2D, total cholesterol, triglycerides, waist circumference, and waist-hip ratio. We found 25 trait-loci associations that met genome-wide significance: 20 previously reported or known associations and 5 putatively new associations via meta-analysis. In particular, with improved statistical power, we were able to confirm the previously suggestive association between the missense CREBRF variant with fasting glucose levels. The remaining 4 potentially novel loci-trait associations for BMI, LDL, and waist-hip ratio, however, were not replicated in All-of-Us. The lack of Polynesian-enriched findings outside of the CREBRF locus informs the bounds of the effect sizes or frequencies of any enriched variants and suggests that further expansion of cohort sizes from this region of the world and improved imputation references specific to these populations are needed to identify more population-enriched associations.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012342"},"PeriodicalIF":3.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of gene regulatory evolution in weapon diversification: Insights from comparative genomics, chromatin profiling, and functional analyses of BMP signaling in horned beetles.","authors":"Phillip L Davidson, Isabel G Manley, Armin P Moczek","doi":"10.1371/journal.pgen.1012338","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012338","url":null,"abstract":"<p><p>Condition-responsive growth is a common feature of multicellular development, during which organisms integrate genetic and environmental signals to adjust their phenotype. However, the molecular properties shaping condition-responsive diversification remain poorly understood. The beetle genus Onthophagus offers promising opportunities to investigate this question, given its diversity of sex- and nutrition-responsive phenotypes, including horns - novel, secondary sexual weapons used in reproductive competition. We compared the gene regulatory properties of horns in two closely related species exhibiting highly specialized sex- and nutrition-biased phenotypes. We found a dynamic cis-regulatory landscape in developing horn tissue, shaped by mutational accumulation across species, condition-specific changes in chromatin accessibility within species, and the acquisition of lineage-specific regulatory elements. Many of these putative regulatory regions include binding site motifs of critical developmental regulatory genes, including members of the bone morphogenetic protein signaling pathway. We provide functional evidence that two proteins in this pathway have been co-opted for horn development, influencing the shape and size of this trait across species, sexes, and nutritional states. These findings provide evidence that evolutionarily labile cis-regulatory interactions may evolve alongside diversification of condition-specific traits, potentially modifying the activity of conserved developmental pathways over short evolutionary timescales.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012338"},"PeriodicalIF":3.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the impact of synthetic ORF sequences on engineered LINE-1 retrotransposition.","authors":"Dorothy Chan, Stephanie Workman, Nathan Smits, Alexander L Carleton, Patricia Gerdes, Jeffrey S Han, Jef D Boeke, Geoffrey J Faulkner, Sandra R Richardson","doi":"10.1371/journal.pgen.1012340","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012340","url":null,"abstract":"<p><p>The retrotransposon Long Interspersed Element-1 (L1) contains adenosine rich open reading frames (ORFs), a characteristic that limits its expression in mammalian cells. A synthetic mouse L1 (smL1) with ORF adenosine content decreased from 40% to 26% showed increased mRNA expression and retrotransposed far more efficiently than the native parental element, L1spa (1). Here, we observe two nonsynonymous substitutions between the L1spa and smL1 ORF1 sequences and note that the smL1 3'UTR lacks a conserved guanosine-rich region (GRR) which could take on a G-quadruplex secondary structure. We find that the combined effect of the altered ORF1p amino acid sequence and the GRR 3'UTR deletion, rather than synthetic ORF sequences, accounts for the increase in smL1 retrotransposition efficiency over L1spa. We determine that inclusion of the GRR influences natural mouse L1 retrotransposition in a position-dependent manner that does not involve premature polyadenylation of L1 mRNA transcripts or alteration of L1 insertion structures. Instead, we present evidence that the position-dependent effect of the GRR on natural mouse retrotransposition occurs through modulation of L1 ORF1p abundance. In contrast, smL1 retrotransposition is refractory to the inhibitory effect of the GRR, likely owing to highly efficient protein expression from synthetic ORF sequences. Taken together, our results prompt further investigation of the relationship between the GRR sequence and L1 protein expression and demonstrate that the arrangement of L1 nucleotide sequences within reporter constructs can influence L1 expression and engineered retrotransposition efficiency.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012340"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLGN3 autism variants have distinct functional impact on synapses and sleep behavior in Drosophila.","authors":"Rebekah E Townsley, Jonathan C Andrews, Saurabh Srivastav, Sharayu V Jangam, Shabab B Hannan, Oguz Kanca, Paul C Marcogliese, Shinya Yamamoto, Michael F Wangler","doi":"10.1371/journal.pgen.1012341","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012341","url":null,"abstract":"<p><p>Neuroligin-3 (NLGN3) was first identified as a X-linked risk gene associated with autism spectrum disorder (ASD). Most reported variants are identified in males who inherited their variants from an unaffected mother, but de novo variants have also been identified in both affected heterozygous females and hemizygous males. The p.R451C variant was the initial variant associating NLGN3 with ASD and has been heavily investigated, yet little is known about the functional consequences of other NLGN3 variants. To determine the functional consequences of other NLGN3 variants in vivo, we generated transgenic Drosophila models corresponding to a de novo variant (p.R175W) identified in a heterozygous female proband with ASD, a maternally inherited variant (p.R451C) identified in a hemizygous male with ASD, and another maternally inherited variant identified in a male (p.R597W) associated with sleep disorder and ASD. In Drosophila, loss of the fly homolog, Nlg3, altered sleep patterns, synaptic architecture, and vesicle dynamics, which were rescued by the expression of the human NLGN3Ref allele. When comparing the variants, the p.R175W variant and the maternally inherited p.R451C variant altered synapse morphology with minimal effects on vesicle dynamics, and the p.R597W variant altered sleep and vesicle dynamics with minimal impact on synapse morphology. Using overexpression models, human NLGN3Ref altered sleep patterns and synaptic morphology. Moreover, the p.R175W variant exacerbated sleep phenotypes, and the p.R175W and p.R451C variants exacerbated synapse morphology phenotypes. Together, our findings suggest that the de novo NLGN3 p.R175W variant identified in a heterozygous female exhibits gain-of-function properties, while maternally inherited variants have context-dependent functional impact. Moreover, some NLGN3 variants disrupt synaptic development, while other variants alter synaptic function, suggesting that NLGN3 variants have differential effects. These functional differences may provide insight into the heterogeneity of individuals with ASD.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012341"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide DNA methylation profiling of tissue-plasma pairs identifies Novel cfDNA biomarkers for the diagnosis of gastric cancer.","authors":"Hailing Ou, Jinli Miao, Fusheng Ling, Jie Gao, Tingan Wang, Zhihua Ye, Chunbo Zhang, Mingwei Huang, Yuzhou Qin","doi":"10.1371/journal.pgen.1012322","DOIUrl":"10.1371/journal.pgen.1012322","url":null,"abstract":"<p><p>Screening for gastric cancer (GC) is critical for improving patient survival, yet current clinical methods suffer from invasiveness and limited sensitivity. The aim of this study is to develop a machine learning model for the non-invasive diagnosis of GC using the whole-genome methylation profile of circulating free DNA (cfDNA) in plasma. Plasma cfDNA from 61 patients with GC and 29 healthy controls. First, whole‑genome bisulfite sequencing (WGBS) was performed on 29 paired GC and adjacent normal tissues to identify differentially methylated regions (DMRs). These tissue DMRs were then mapped to plasma cfDNA methylation data, yielding 32 stable DMRs that changed consistently in both tissues and plasma. Using LASSO and Random Forest (RF) algorithms, eight core diagnostic markers were selected. Four machine learning algorithms (Support Vector Machine, RF, K-Nearest Neighbor, Naïve Bayes) were used to build diagnostic models. WGBS revealed global hypomethylation and CpG island hypermethylation in GC, consistent with plasma cfDNA methylation patterns. The RF model built on the eight cfDNA methylation markers (annotated to genes including ATP8A2) performed best, achieving AUC values of 0.978 and 0.938 in the training and independent test sets, respectively, with an accuracy of 88.46%, sensitivity of 94.44%, and specificity of 75.00%. After adjusting for age, the model achieved an AUC of 0.924 on the test set, still demonstrating high discriminatory performance. Functional analysis implicated these markers in pathways such as phagocytosis and axon guidance, and showed significant correlation with immune cell infiltration. Notably, these core DMRs are not covered by the probes on the methylation arrays (450K and EPIC v2), highlighting the advantage of WGBS for novel biomarker discovery. In conclusion, tissue-plasma concordance analysis identified a panel of plasma cfDNA methylation biomarkers with strong diagnostic potential. The resulting RF model provides a promising non-invasive strategy for GC screening.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012322"},"PeriodicalIF":3.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversification and functional expansion of archaeal T4F machineries.","authors":"Shamphavi Sivabalasarma, Sonja-Verena Albers","doi":"10.1371/journal.pgen.1012139","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012139","url":null,"abstract":"<p><p>Archaea have several cell surface structures belonging to the type 4 filament (T4F) superfamily. All share a minimal core assembly system consisting of an ATPase, a platform protein, a filament-forming protein, and a class III signal peptidase. Here, we generated novel MacSyFinder2 models to identify and classify archaeal T4F systems. Our analysis revealed a vast diversity of archaeal T4F, with many organisms harboring one or more assembly machineries. Structure-based phylogenetic analysis showed that the variable N-terminal domain of T4F-related ATPases mirrors the subsystem clustering, indicating that the core machinery has diversified within the archaeal secretion ATPase family through structural innovation. Genome-wide screening for signal peptidase III cleavage site (SPIII) containing proteins revealed the widespread presence of substrate-binding proteins carrying a class III signal peptide. We propose that these binding proteins, with canonical SPIII cleavage sites, functionalize T4F machineries for efficient substrate scavenging, expanding the functional repertoire of archaeal T4F systems beyond their currently characterized roles.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012139"},"PeriodicalIF":3.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}