Biology subjects

McGrath, H.

Publications and source records attributed to McGrath, H..

4 recordsLinked to original sources

bioRxiv2026

Genomic detection of domoic acid biosynthesis uncovers expanded toxigenic diversity across Pseudo-nitzschia diatoms

Domoic acid (DA) production by diatom genus Pseudo-nitzschia causes recurrent harmful algal blooms with major consequences for marine ecosystems, fisheries, and human health. Predicting DA risk remains challenging because toxin production varies across morphologically similar and cryptic lineages. Consequently, morphology or single marker genes often fail to resolve toxigenic potential. Here, we expand genomic resources for Pseudo-nitzschia by generating and compiling high-quality genomes spanning diverse species and biogeographic origins, establishing a genus-wide phylogenomic framework to investigate the distribution and evolution of the DA biosynthesis (dab) gene cluster. Among chemically characterized strains, the dab pathway was detected in species only with confirmed DA production. While the cluster exhibits a conserved core structure, several lineages display signatures of ongoing evolution, including intronization, locus rearrangement, and pseudogenization. One striking example of dab variation occurs in toxigenic P. australis strains, in which its biochemically validated isodomoic acid A synthase-encoding gene dabC is located outside the dab locus. Metatranscriptomic surveys reveal widespread environmental dab expression across size classes and species, implicating taxa not typically associated with environmental DA events, such as P. cf. obtusa and P. cf. plurisecta. To connect dab expression with chemical output, nutrient limitation experiments in the historically inconsistent DA producer P. pseudodelicatissima combined transcriptional profiling and nontargeted metabolomics demonstrating coordinated dab expression across distinct co-expression modules and DA accumulation in response to silicon limitation. Together, these results refine the phylogenetic scope of DA production and provide a genome-resolved basis for improved molecular monitoring of toxigenic diversity.

genetics↗

bioRxiv2026

Ribosomes are covered by a coat of flexible protein fragments

Ribosomal proteins contain flexible terminal regions that are averaged out during electron density reconstructions, rendering them absent from experimental models derived by X-ray crystallography or cryogenic electron microscopy. These flexible protein fragments (FPFs) collectively form an invisible coat on the ribosome surface whose presence has been systematically overlooked. Here we analysed FPFs from 36 ribosomes spanning bacteria, eukaryotes, and mitochondria. We found that mitoribosomes harbour the most numerous and longest FPFs. Structural predictions confirmed that FPFs are predominantly disordered across all ribosome classes. Comparison of FPF amino acid composition against proteome-wide background frequencies revealed strong and domain-specific compositional biases. The balance between arginine and lysine content tracks the cardiolipin content of the membrane each ribosome class contacts. The arginine enrichment in mitoribosomal FPFs may additionally reflect selection arising from the RNA-rich environment of mitochondrial RNA granules, membraneless condensates where mitoribosomes are assembled. FPFs are uniformly depleted in aromatic residues, arguing against protein-driven liquid-liquid phase separation propensity. Our findings suggest that the flexibly tethered coat is a highly functional intrinsic part of all ribosomes.

bioinformatics↗

bioRxiv2026

Early nascent polypeptide dynamics are coupled to the flexibility of the ribosomal tunnel constriction

The ribosomal exit tunnel, through which all nascent polypeptides emerge, is formed primarily by ribosomal RNA. Still, ribosomal proteins contribute roughly one quarter of the tunnel walls. In particular, proteins uL4 and uL22 define the narrowest region of the tunnel. This constriction, enriched in basic residues, mediates the earliest protein-protein contacts experienced by a nascent polypeptide. Here, we characterize its conformational dynamics by analyzing 222 Escherichia coli ribosome structures from the Protein Data Bank and by performing unbiased all-atom molecular dynamics simulations of the complete bacterial ribosome with nascent polypeptides of varying length and composition. In simulations of the empty ribosome, the constriction can transiently narrow below the diameter of a water molecule and thus fully occlude the tunnel. At other times it opens wide enough to accommodate a narrow -helix. The presence of even a short nascent polypeptide shifts the constriction toward wider conformations by approximately 0.2 nm, revealing an adaptive response of the tunnel to its contents. Across all simulated systems, the N-terminal formylmethionine preferentially associates with the tunnel wall at the uL22 side. Our findings replace qualitative description of the tunnel dynamics with a quantitative one. The constriction site functions as a flexible gate, with implications for nascent polypeptide translocation, action of macrolide antibiotics, and the translational ramp.

biophysics↗

bioRxiv2022

Binding of the peptide deformylase on the ribosome surface modulates the structure and dynamics of the exit tunnel interior

Proteosynthesis on ribosomes is regulated at many levels. Conformational changes of the ribosome, possibly induced by external factors, may transfer over large distances and contribute to the regulation. The molecular principles of this long-distance allostery within the ribosome remain poorly understood. Here, we use structural analysis and atomistic molecular dynamics simulations to investigate peptide deformylase (PDF), an enzyme that binds to the ribosome surface near the ribosomal protein uL22 during translation and chemically modifies the emerging nascent peptide. Our simulations of the entire ribosome-PDF complex reveal that the PDF undergoes a swaying motion on the ribosome surface at the sub-microsecond time scale. We show that the PDF affects the conformational dynamics of parts of the ribosome over distances of more than 5 nm. Using a supervised-learning algorithm we demonstrate that the exit tunnel is influenced by the presence or absence of PDF. Our findings suggest a possible effect of the PDF on the nascent peptide translocation through the ribosome exit tunnel.

biophysics↗