Biology subjects

Yin, Y.

Publications and source records attributed to Yin, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Human hindbrain organoids with segment-specific 5-HT neurons for motor modulation

The serotonergic system regulates human mood, reward, and motor control, and its impairment contributes to debilitating psychiatric disorders. Serotonergic neurons (SNs) arise predominantly in the hindbrain and acquire segment-specific identities and functions; however, the lack of human models remains a challenge to understanding the human serotonergic system. Here, we generate human serotonergic-enriched rostral and caudal hindbrain organoids (hsrHOs and hscHOs) that produce segment-specific SNs with regional identities corresponding to rhombomeres r2-r3 and r5-r8, respectively. hsrHOs and hscHOs produce SNs that recapitulate their in vivo counterparts in transcriptomic profiles, function, and ascending or descending projection preferences. Assembly with human neuromusculoskeletal organoids enables modeling of serotonergic modulation of motor control. This system further reveals that deficiency of the schizophrenia risk gene DISC1 disrupts human serotonergic development and impairs motor modulation. Together, our study establishes a human organoid platform for modeling development, circuit function and disease-associated dysfunction of the serotonergic modulatory system.

neuroscience↗

bioRxiv2026

Lesions initiating spontaneous mitotic crossover are minimally subject to non-homologous end joining

Homologous recombination (HR) between sister chromatids is the dominant outcome of replication-associated DNA repair, yet the lesions that initiate spontaneous mitotic crossovers remain poorly defined. Most mechanistic work on HR pathway choice uses enzymatically induced two-ended double-strand breaks (DSBs), where non-homologous end joining (NHEJ) is a major competing pathway. Whether NHEJ also competes for spontaneous, replication-associated lesions has not been directly tested. Here we use sci-L3-Strand-seq, a single-cell replication-template strand-specific sequencing method that maps sister chromatid exchange (SCE) genome-wide, to profile heterozygous and homozygous knockouts of NHEJ factors (LIG4, XRCC4) and the single-strand break (SSB) repair scaffold XRCC1 in HAP1 and BJ cell lines. NHEJ disruption produced only a modest (30%) increase in SCE, whereas XRCC1 loss caused a pronounced, 5-fold elevation. The dense, widespread SCE pattern in XRCC1-deficient cells is consistent with unrepaired SSBs being converted at replication forks into one-ended DSBs that lack a second end for ligation and therefore cannot engage NHEJ. In parallel, structural variation (SV) mapping in the same single cells revealed a strongly non-random landscape dominated by recurrent chromosome losses and clonal expansion, indicating selective pressure and stepwise genome evolution. SCE frequency did not correlate with SV burden or SV-defined subclones, demonstrating that error-free recombination and mutational rearrangement represent separable axes of genome maintenance. Recovery of reciprocal daughter-cell pairs with matching SCE breakpoints directly confirms that these events arose by inter-sister exchange in the preceding division. Together, these results show that spontaneous mitotic crossovers are driven by lesions largely incompatible with NHEJ and instead engage HR through replication-coupled SSB-to-DSB conversion, and that elevated error-free recombination is decoupled from the mutational SV landscape.

genomics↗

bioRxiv2026

Genome-wide mapping of Cas9-induced sister chromatid exchange across single and over 200 genomic targets

CRISPR/Cas9-induced DNA double-strand breaks (DSBs) are widely used for genome engineering, yet their capacity to provoke sister chromatid exchange (SCE) and associated genome instability remains incompletely understood, in part because exchanges between identical sister chromatids leave no sequence change and are invisible to conventional whole-genome sequencing. Using sci-L3-Strand-seq, a scalable single-cell template-strand sequencing platform for genome-wide SCE mapping, we quantified strand-switch events following targeted Cas9 cleavage. Cas9 targeting of a unique genomic locus led to strong local enrichment of SCE at the break site, reaching up to 41% in the same cell cycle and 17% in the subsequent division, indicating that DSB repair frequently engages non-local inter-sister repair. Extending the assay to 237 repetitive Alu targets using one Alu-specific sgRNA revealed mild and marginally statistically significant enrichment of on-target SCE across wild-type Cas9 and nickase variants (D10A and H840A). However, restricting analysis to a subset of cells with elevated SCE burden (>8 SCEs per cell) uncovered significant enrichment at programmed cut sites, suggesting that recombination at repetitive loci is conditionally engaged in highly recombinogenic cells. Reciprocal daughter-cell pair analysis further revealed large-scale structural alterations on chromosomes with induced SCEs and at SCE junctions, indicating that Cas9-induced SCEs do not universally reflect error-free homologous recombination. Disruption of DNA repair genes at the cut site, including LIG3, LIG4, XRCC1, and XRCC4, did not measurably alter SCE frequency per cell, consistent with delayed functional loss following editing and, in the case of essential genes such as LIG3, selection against disruptive alleles. Together, these findings demonstrate that Cas9-induced DSBs are potent local triggers of SCE at unique loci, while at repetitive regions SCE is more context-dependent and can be associated with structural alterations, highlighting the influence of lesion type and genomic context on recombination outcomes during genome editing.

genomics↗

bioRxiv2026

Causally validated phase-amplitude coupling enables high-fidelity motor decoding for next-generation brain-computer interfaces

Modern Brain-Computer Interfaces (BCIs) face a fundamental performance plateau due to their reliance on broad spectral power reduction (Event-Related Desynchronization, ERD) as the primary decoding feature. ERD acts as a coarse metabolic proxy for cortical activation, discarding the high-frequency temporal syntax necessary for high-dimensional motor control. Here, we demonstrate that Phase-Amplitude Coupling (PAC)--specifically, the phase-locking of high-gamma (70-150 Hz) firing to residual Beta oscillations--provides a high-fidelity temporal feature for decoding motor intent. Using high-density electrocorticography (HD-ECoG) during motor imagery, we show that incorporating Beta-PAC into machine-learning classifiers (LDA/SVM) significantly outperforms traditional power-based features. To definitively validate the causal robustness of this feature against mathematically-derived artifacts, we leveraged a rare in vivo human structural lesion model. In a patient with focal tumor infiltration of the motor tract, the metabolic gate (ERD) was preserved, yet structural uncoupling completely abolished Beta-PAC, collapsing network topology and reducing single-trial decoding accuracy to chance levels. Our findings causally validate Beta-PAC as a robust, independent control signal, establishing a physiological foundation for next-generation, phase-dependent neuroprostheses.

neuroscience↗

bioRxiv2026

Epigenetic and 3D Genome Changes Drive Primary Trastuzumab Resistance in HER2+ Breast Cancer

Primary trastuzumab resistance remains a major challenge in the treatment of HER2-positive breast cancer, with limited therapeutic options highlighting the need for deeper mechanistic insight. Here, integrative analysis of epigenomic and three-dimensional chromatin architecture reveals widespread remodeling of the regulatory landscape in resistant cells. Alterations in promoter-associated histone modifications?particularly H3K4me3 and H3K27me3?together with changes in active enhancer activity and promoter-enhancer interactions, appear to be key drivers of transcriptional reprogramming underlying resistance. As an illustrative example, SGK1 exhibits epigenetic activation in resistant cells, characterized by increased promoter H3K4me3 and enhanced chromatin interactions, consistent with its role in supporting cell survival, proliferation and metastasis. Overall, our findings highlight epigenetic and chromatin structural alterations as central mechanisms of primary trastuzumab resistance, providing a framework for novel therapeutic strategies development.

cancer biology↗

bioRxiv2026

Rewiring Oncogenic Transcriptional Complexes with Domain-ALTeration Chimeras (DALTACs) in Prostate Cancer

Transcriptional addiction to the androgen receptor (AR) underlies metastatic castration-resistant prostate cancer (mCRPC), where AR maintains oncogenic programs through domain-specific interactions with the acetyltransferases p300/CBP. Here, we describe a distinct therapeutic modality, Domain-ALTerAtion Chimeras (DALTACs), that rewire endogenous protein complexes by enforcing non-native domain-domain interactions. Our first-in-class AR-p300/CBP DALTAC-1 induces synthetic proximity between the AR ligand-binding domain and p300/CBP-bromodomain, misconfiguring their native interface and locking the complex in a non-productive state. DALTAC-1 triggers a super-inhibitory effect, suppressing AR-driven transcription and proliferation more potently than combined AR and p300/CBP inhibition. Mechanistically, DALTAC-1 reprograms p300/CBP substrate engagement, abolishing the histone mark H2B N-terminal acetylation (H2BNTac) while inducing neomorphic acetylation of AR and coactivators, ultimately collapsing the AR neo-enhanceosome. Chromatin profiling revealed redistribution of AR and p300/CBP toward palindromic AREs, accompanied by disruption of cofactor and transcriptional machinery recruitment at oncogenic AR/ERG neo-enhancers. DALTAC-1 exhibits exquisite lineage selectivity, displaying potent activity in AR-p300/CBP dual-dependent cells while sparing AR-negative cells. In multiple in vivo models, DALTAC-1 induces deep and durable tumor regressions. Together, these findings establish DALTACs as a broadly applicable strategy to rewire disease-defining complexes through domain-topology alteration, expanding induced-proximity therapeutics, while DALTAC-1's precise lineage-selectivity supports its translational potential in AR-driven prostate cancer.

cancer biology↗

bioRxiv2026

Curvature-mediated prewetting organize mitochondrial nucleoid

The emergence of spatiotemporal order in diffusive cellular environments requires physical mechanisms to overcome the entropic drive toward disorder. While the organizing role of chemical signaling is well characterized, how complex membrane curvature regulate soluble molecular organization remains a fundamental open question. Here, we establish membrane curvature as a thermodynamic control parameter for the condensation of soluble proteins through prewetting. Using the mitochondrial transcription factor TFAM, we demonstrate that intrinsic membrane curvature locally drives a prewetting transitiona surface-mediated phase separation distinct from bulk condensation. By combining in vitro reconstitution, live-cell super-resolution imaging, cryo-electron tomography, and thermodynamic theory, we show that negatively high-curvature regions lower the nucleation energy barrier of Tfam, driving localized protein condensation at physiological concentrations. These results reveal that membrane curvature does not merely scaffold cellular machinery but manipulates the local free energy landscape, establishing a geometric principle for the spatial control of biological processes.

biophysics↗

bioRxiv2026

AI predictions and the expansion of scientific frontiers: Evidence from structural biology

Artificial intelligence holds the potential to expand the frontier of scientific research, yet recent work has raised concern that it may instead narrow scientific attention to well-established areas. Here, leveraging the 2021 release of AlphaFold2 as a quasi-experimental opportunity, we provide field-level evidence that AI can redirect collective attention toward more novel research targets. Tracking 245,396 experimental structures in the Protein Data Bank, we show that a long-running decline in the study of novel proteins halted after AlphaFold2s release, with the shift concentrated among studies citing AlphaFold2 and targets with high-confidence predictions. This pattern extends to 248,191 downstream papers that consume structural knowledge, where engagement with genes lacking experimental structures and with understudied human genes increased since 2021. Amid rising concern that AI may reinforce scientific canons, our findings offer an early field-level case where AI predictions expand scientific frontiers, consistent with the idea that the real-world consequences of AI on science depend on where their informational gains are greatest. These results suggest AI can complement human knowledge and redirect collective attention in science, with broad implications for emerging AI for science models.

bioinformatics↗

bioRxiv2026

TRiC folds the giant ciliary protein IFT172 via a non-canonical open-state mechanism

The eukaryotic chaperonin TRiC/CCT is essential for folding complex proteins, yet how it folds substrates that exceed its closed chamber capacity remains a longstanding paradox. Here, we define the folding pathway of IFT172, the largest subunit ([~]200 kDa) of the intraflagellar transport (IFT) machinery, and uncover a "divide-and-conquer" mechanism. TRiC and HSP70 engage IFT172 concurrently but on distinct domains: TRiC captures the N-terminal WD40 {beta}-propellers within its chamber, whereas HSP70 independently stabilizes the C-terminal TPR domain in the cytosol. To accommodate this oversized client, specific TRiC subunits (CCT4, CCT2, and CCT7) undergo pronounced Z-shaped outward bending, thereby expanding the chamber. Unexpectedly, the first WD40 domain reaches a near-folded state within the open, ATP-bound chamber, and subsequent TRiC ring closure triggers substrate ejection rather than encapsulation. This non-canonical "fold-and-eject" mechanism challenges the classical view that the closed chamber is an obligate folding cage. We further demonstrate that this pathway is essential for ciliary functions in vivo, and reveal a conserved mode of chaperonin recognition among IFT components bearing tandem WD40-TPR architectures. Together, our findings establish a new paradigm for the folding of oversized, multi-domain proteins and identify TRiC as a central proteostasis hub in ciliary biogenesis, with direct implications for ciliopathy pathogenesis.

biochemistry↗

bioRxiv2026

Nuclear speckle protein SON safeguards efficient splicing of GC-rich genes

Gene architecture in higher eukaryotes exhibits substantial heterogeneity. While most genes follow a canonical pattern of GC-rich exons and AT-rich introns, a subset displays GC-leveled architecture, characterized by uniformly high GC content across both exons and introns. These genes are often associated with nuclear speckles, membraneless compartments enriched in RNA-processing factors, yet the mechanistic basis of this spatial and functional relationship remains unclear. Here, we identify the nuclear speckle protein SON as a critical factor that safeguards the splicing of GC-rich genes. Acute depletion of SON in mouse embryonic stem cells selectively impairs the splicing of short, GC-rich introns. These SON-dependent introns are enriched in highly expressed and functionally essential genes, whose GC-rich architecture contributes to efficient RNA processing and expression. Mechanistically, these introns harbor atypical C-rich, U-poor polypyrimidine tracts at their 3 splice sites, which exhibit reduced affinity for core splicing factors. SON is recruited to these sites via U2 snRNP and further interacts with SR proteins to stabilize the association of U2 snRNP and U2AFs at these C-rich weak splice sites. Notably, the evolutionary expansion of SONs intrinsically disordered region is required to promote efficient splicing of GC-rich genes that emerged during evolution. Together, our study suggests that the evolutionary transition toward GC-rich gene architecture enhances gene expression efficiency, with SON acting to safeguard the splicing of this gene class.

molecular biology↗

bioRxiv2026

Sex-specific Genetic Regulatory Effects in Chickens

Sexual dimorphism is a defining vertebrate feature, yet its sex-specific molecular architecture remains poorly understood. Here we established a sex-balanced, uniformly reared chicken cohort to map this landscape, integrating individual whole-genome sequencing with 7,969 bulk and 779,380 single nucleus transcriptomes across 32 tissues from 280 birds. We identified 495,098 independent expression quantitative trait loci for 20,194 genes, including 10,937 loci modulated by cell-type composition. Notably, 340 genes were regulated by 449 loci in a sex-dependent manner, significantly enrichment in endocrine tissues like adipose and the adrenal gland. Furthermore, we fine-mapped 1,219 structural variants, demonstrating their unique roles to tissue- and sex-specific expression beyond SNPs. Ultimately, we showed the utility of these regulatory effects in elucidating the molecular basis of metabolism and complex traits in both chickens and humans. This comprehensive atlas of regulatory effects provides profound insights into the genomic and molecular basis of sexual dimorphism in vertebrates.

genomics↗

bioRxiv2026

Pharmacological recruitment of a VTA glutamatergic arousal circuit by the natural product BN3 drives broad-spectrum emergence from general anesthesia

Pharmacological control of emergence from general anesthesia remains strikingly limited. Clinically available antagonists are largely drug-class specific, leaving recovery dependent on anesthetic clearance rather than to an actively programmable switch in brain state. Through phenotypic screening of a structurally diverse natural-product library, we identified BN3 (L-(-)-camphor) as a broad-spectrum emergence agent. BN3 robustly shortened recovery from propofol anesthesia across species--from mice and rats to rabbits, dogs, and rhesus monkeys--and remained effective after continuous infusion. In rodents, BN3 also accelerated emergence from mechanistically distinct anesthetics, including etomidate, remimazolam, sodium {gamma} - hydroxybutyrate, midazolam, ketamine, sodium pentobarbital, and isoflurane. EEG recordings revealed a rapid cortical shift from slow-wave dominance to a wake-like high-frequency spectrum. Mechanistically, BN3 preferentially recruited ventral tegmental area (VTA) glutamatergic neurons: chemogenetic silencing abolished the BN3-evoked EEG spectral shift and strongly attenuated behavioral acceleration of emergence, whereas optogenetic activation of these neurons was sufficient to promote recovery. BN3 increased glutamate release in the nucleus accumbens and medial prefrontal cortex, and projection-specific inhibition of VTA[->]NAc or VTA[->]mPFC outputs blunted BN3-induced emergence. These findings define a VTA-centered glutamatergic arousal circuit that can be pharmacologically recruited as a common gateway for anesthetic-independent emergence.

neuroscience↗

bioRxiv2026

Evolutionary dynamics of insect odorant receptors reveal ecological tuning shaping olfactory perception

Insect olfaction is facilitated by a heterotetrameric odorant receptor-odorant receptor co-receptor (OR-Orco) complex, which is distinct from that of vertebrate ORs. However, extreme sequence divergence among insect ORs has hindered a unified understanding of their evolutionary history and ecological importance. In this study, we present a multiscale analysis of OR genes across 115 insect species. We overcome the limitations of traditional phylogenetic approaches by applying a protein similarity network-based strategy and introduce a "trunk-branch" framework to systematically describe the evolutionary trajectories of insect ORs across sequence, structural, and predicted olfactory potential levels. Although they possess different sequences and structural communities, all sampled insect orders contained ORs assigned to all six docking-derived functional communities. Notably, extant insect lineages with order-level origins spanning the end-Permian mass extinction (EPME) differed in docking-derived functional OR repertoires, and early-and late-diverging lineages differed in OR sequence-community diversity. The emergence of Orco represents a key evolutionary transition point, marking the shift from a homomeric to a heteromeric complex accompanied by specialization of the extracellular domain and binding pocket. Furthermore, we established robust associations between potential olfactory recognition breadth and ecological variables, including diet, circadian rhythm, and habitat. Our findings provide a class-level framework for investigating insect OR evolution and generate testable hypotheses about how receptor repertoire diversification may relate to ecological adaptation.

evolutionary biology↗

bioRxiv2026

Construction and Immunogenicity Detection of Canine Parvovirus-like Particles Fusion with Canine Febrile Antigen Epitopes

This study aimed to design and evaluate the immunogenicity of a dual-valent virus-like particles (VLP) vaccine that can simultaneously target Canine distemper virus (CDV) and Ca nine parvovirus virus (CPV).By bioinformatic analysis, conserved antigen epitopes of the three major functional proteins of CDV were screened and inserted into CPV-VP2 proteins by two different methods to construct recombinant expression plasmids CDPV1 versus CDPV2.Thr ee-dimensional structure, hydrophobicity and stability predictions of the two recombinant proteins showed that their hydrophobicity were 0.233 and 0.251, and their structural stability scores were 0.77 and 0.78, respectively.Recombinant plasmids were co-transformed with molecular chaperone pTf16 to be expressed in E. coli BL21(DE3), respectively, and the optimal expression conditions were determined after optimization: 0.25 mmol/L IPTG, 2 g/L L-arabinose in duction, and culture at 25{degrees}C for 16 h.Purified recombinant proteins can self-assemble in vitro to form VLPs about 23.5 nm in diameter with a hemagglutination titer of 1:29.The mouse immune test showed that the hemagglutination inhibition titer peaked on the 7th day after the third immunization, and the neutralizing Antibody level could reach up to 1:28.The CPV VLP s constructed in this institute carrying CDV antigen epitopes were able to successfully assemble in vitro and were well immunogenic, providing experimental basis for the development of a canine polyvalent vaccine.

immunology↗

bioRxiv2025

Carbon bias from grassy tree misclassification: revealing forest structural heterogeneity by integrating GEDI and Sentinel-2

Tropical forests store roughly half of terrestrial carbon, yet carbon estimates in regenerating and disturbed forests remain highly uncertain. A major source of bias is the prevalence of fast-growing, canopy-forming monocots--such as bamboo, palms, and bananas--that are often misclassified as trees. These "grassy trees" achieve canopy dominance but lack secondary growth, violating woody allometries used in most biomass models. Although NASAs GEDI mission has transformed large-scale biomass mapping with spaceborne LiDAR, its products rely on coarse plant functional types (PFTs), causing grassy-tree-dominated canopies to be absorbed into evergreen broadleaf tree (EBT) classes. Using a texture-based Sentinel-2 classifier, we isolated bamboo-dominated forests within GEDI EBT products in Xishuangbanna, China. GEDI observations show that bamboo canopies are structurally distinct from tree-dominated forests and lead to systematic carbon overestimation of 20-44 Mg C ha-{superscript 1} relative to empirical benchmarks. Our framework improves carbon accounting in structurally heterogeneous forests while remaining adaptable for place-based management.

ecology↗

bioRxiv2025

Tirzepatide Synergizes with Leptin on Weight Loss and Restoring Metabolic Homeostasis in Diet-induced Obesity Model

Leptin resistance limits anti-obesity efficacy. We identified a leptin-sensitizing mechanism through tirzepatide (TZP), a glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonist. Our tirzepatide clinical trial revealed that circulating leptin levels at baseline correlated with weight loss efficacy in patients with obesity, suggesting leptin and tirzepatide could interact to achieve stronger effects on weight loss. Next, we utilized the diet-induced obesity (DIO) mice and demonstrated the synergistic effects of tirzepatide and leptin combination (TZP+Lep) on weight loss. TZP+Lep treatment further improved hepatic insulin sensitivity and upregulated thermogenetic gene expression in brown adipose tissue. Metabolic profiling under thermoneutrality revealed TZP+Lep treatment further reduced food intake and increased energy expenditure. Tirzepatide sensitized leptin signaling in hypothalamic pro-opiomelanocortin (POMC) and GLP-1R expressing neurons. TZP+Lep synergistically increased POMC neuronal firing by decreasing the inhibitory postsynaptic input. Together, our work showed combining tirzepatide and leptin as a potential way for better maintenance of metabolic homeostasis in obesity management. HighlightsO_LITirzepatide and leptin synergistically promote weight loss through reduced food intake and increased energy expenditure. C_LIO_LITirzepatide and leptin synergistically improve insulin sensitivity and metabolic homeostasis with altered hepatic and adipose gene expression. C_LIO_LITirzepatide sensitizes leptin signaling in hypothalamic GLP-1R and POMC neurons. C_LIO_LITirzepatide and leptin synergistically increase POMC neuronal firing by decreasing inhibitory postsynaptic input. C_LI

neuroscience↗

bioRxiv2025

LRP8 is a Receptor for Yellow Fever Virus

Yellow fever virus (YFV), an arbovirus causing substantial human morbidity and mortality, was the first human virus discovered over a century ago. The live-attenuated 17D vaccine is among the most successful vaccines in medicine. Despite the importance of YFV, its receptor has remained unknown. Here, we performed a barcoded, genome-wide human ORF library screen and identified LRP8 (also named APOER2) as a receptor for YFV. We show that LRP8 expression specifically boosts YFV infection in cell lines by promoting entry. AAV-mediated expression of human LRP8 in mouse liver aggravates infection and pathology. LRP8 knockdown abolishes YFV infection in brain cells, primary human hepatocytes, and notably in mosquitoes. Biochemically, LRP8 directly interacts with YFV particles via the viral envelope protein. This function of LRP8 is conserved across species, particularly in mosquitoes and primates. A soluble LRP8 decoy protein can block YFV infection in vitro and in mice, providing a potential therapeutic or prophylactic strategy. Our findings provide groundwork for understanding YFV entry, tropism, and pathogenesis, and may enable development of novel therapeutics to treat YFV infection.

microbiology↗

bioRxiv2025

Mucinolysome in gut microbiomes of farm animals and humans

Mucins are glycoproteins that create a protective barrier protecting host tissues from microbial pathogens and are instrumental for host health. Here, we provide evidence that mucin glycan degradation in the gut can be mediated by mucinolysomes, defined as extracellular multi-enzyme complexes specializing in mucin glycan degradation. We computationally predicted the presence of mucinolysomes across 63 metagenome-assembled genomes (MAGs) and two isolated genomes of anaerobic Limousia bacteria, including seven MAGs from human samples of six countries. All 65 genomes were found to display core mucinolysome components, consisting of 3[~]6 scaffoldins (containing up to 12 cohesin modules) and up to 22 dockerin-containing mucin glycan-degrading CAZymes (carbohydrate active enzymes). The organization of mucinolysomes allows the assembly of up to 24 CAZymes in the same complex. We validated that a cultivated Limousia strain ET540 from chicken cecum can support growth on mucins as its sole carbon source, triggering the expression of most mucinolysome-related genes, including both scaffoldins and CAZymes. We also modeled the assembly of proteins into a multi-enzyme complex by predicting the cohesin-dockerin interactions among most of the mucinolysome proteins using AlphaFold3. While mucinolysosome-encoding Limousia have low abundance in different animal hosts, their abundance and prevalence are higher in farm animals than in humans, highlighting a potentially important role in livestock gut ecosystems. Our findings reveal a novel mechanism of mucin glycan degradation and provide a framework to explore microbial contributions to gut health and host-microbe interactions across species.

bioinformatics↗