Anti-CRISPR (Acr) proteins have evolved in bacteriophages and mobile genetic elements to counteract CRISPR-Cas immune systems through diverse inhibitory mechanisms. Here, we present the crystal structure of AcrIIA17 and elucidate its mechanism of Staphylococcus aureus Cas9 (SauCas9) inhibition. AcrIIA17 adopts a previously uncharacterized protein fold and exists as a monomer in solution. Biochemical analyses reveal that AcrIIA17 inhibits SauCas9 activity in a strictly order-dependent manner, effectively suppressing DNA cleavage only when it engages Cas9 prior to single guide RNA (sgRNA) loading, whereas pre-assembled Cas9-sgRNA ribonucleoprotein (RNP) complexes are resistant to inhibition. Domain-mapping experiments demonstrate that AcrIIA17 directly binds to the bridge helix (BH) domain of SauCas9, and structure-guided mutagenesis confirms that this interaction is essential for its inhibitory function. Together, our findings identify AcrIIA17 as an Acr protein that targets the Cas9 BH domain and reveal the BH domain as a regulatory checkpoint in Cas9 activation.
This study constructed a pH-responsive P-TN/SF@Fe-Cur composite coating that demonstrated significant anti-infective, anti-inflammatory, antioxidant, pro-angiogenic, and pro-osteogenic effects in rat subcutaneous infection and femoral defect models.
ProteinReasoner is developed, a multimodal generative protein foundation model that sequentially connects amino acid sequence, evolutionary constraints and three-dimensional structure within a shared autoregressive architecture and suggests a general route towards reasoning across interdependent representations in other scientific domains.
Chaozhong Liu, Linlin Chao, Shaomin Ji et al.· bioRxiv· 1 citation
Due to its importance and wide adoption, wheat cultivation is promptly required to shift towards sustainable practices, reducing the dependency on chemical components. Among bio-based solutions aimed at securing the sustainability of wheat cultivation, biostimulants offer a versatile platform of eco-friendly tools assuring sustainability and profitability. Microalgae present a concrete example of a biostimulant source due to their richness in metabolites and high value products. Therefore, this study evaluated the biostimulant potential of eleven eco-extracts prepared from soil-isolated microalgae strains. Eco-extracts applied via soil drench at low dose (0.1 g/L) were investigated for their biostimulant effects on wheat growth, physiology, yield, and quality under controlled conditions. Results demonstrated significant ameliorations in treated plants as compared to the control, with no phytoinhibitory effects. Remarkable enhancements were notable in growth parameters such as shoot and root lengths (+40-70%), physiological traits such as total chlorophyll and stomatal conductance (+7-52%), yield components in the example of grain number per spike and thousand grain weight (+17-103%), and grain quality namely protein and polyphenol content (+2-fold to 4-fold). Similarly, phosphorus accumulation and uptake were significantly improved, while soil physicochemical status was ameliorated, indicating enhanced fertility. Multivariate analysis and composite index ranking marked Chlorella sp. GA18, Chlorella sp. GA65, Scenedesmus sp. GA69, and Chlorococcum sp. GA63 as eco-extracts with consistent performances across all plant traits. These findings highlighted the promising potential of integrating microalgae-based eco-friendly extracts in sustainable wheat cultivation.
Amer Chabili, Z. Hakkoum, F. Minaoui et al.· Plant Science· 1 citation
HydroGym is introduced, a solver-independent reinforcement learning platform providing more than 60 validated, openly available flow control environments spanning from canonical laminar flows to complex turbulent flows, with systematic progression in the Reynolds number up to Re = 4 × 105, and Mach number variations in two and three dimensions.
Christian Lagemann, Sajeda Mokbel, Miro Gondrum et al.· Nature· 1 citation
ABSTRACT Microplastics (MPs) accumulation in ecosystem and human organs poses urgent environmental and health risks, yet few enzymes efficiently degrade polyethylene terephthalate (PET) under physiological conditions. We leveraged deep learning to mine unexplored sequence space across 246 million proteins, discovering AhPETase, an evolutionarily distinct hydrolase with low homology (<50% sequence identity) to known PET‐degrading enzymes. This noncanonical biocatalyst efficiently depolymerizes PET at 37°C, outperforming all typical PETases and achieving a 7.76‐fold enhancement over IsPETase, one of the most representative mesophilic PETases. Additionally, engineered variant AhPETaseM1 retains functional activity for over 20 days under physiological conditions and can degrade post‐consumer PET MPs 34‐fold faster than recombinant human‐derived enzyme MG8 (rMG8) under equal enzyme loading. Critically, it reversed PET‐induced toxicity in human lung and colon cells, establishing the first proof‐of‐concept for enzymatic MPs detoxification.
Yuxuan Wang, Shijie He, Yuheng Chang et al.· Advancement of science· 0 citations
Histone proteins play a central role in chromatin organization. In eukaryotes, the fundamental units of DNA packagingthe nucleosomal coresare assembled from histone dimers. The double histone fold (DHF) refers to a protein architecture in which two adjacent regions, each containing a histone fold, associate to form a histone pseudodimer. In the present study, by targeted sequence searches in protein databases and subsequent structural and phylogenetic investigations, we identified a large number of DHF proteins featuring a high or very high degree of identity with the amino acid sequences of both histones H3 and H4, which constitute a new class of eukaryotic DHF proteins. Strikinglysomehow in analogy with recently identified proteins encoded in some giant viruseswe found, as well, triplets of various kinds (i.e., proteins showing regions of homology with histones H3, histone H4, and an additional histone fold). We were also able to evidence the existence of unprecedented quadruplets encompassing two distinct DHF domains, as well as multiplets that include not only region of homology to nucleosome core histones, but also to the linker histone H1. Focus was put on the evolutionary scenarios for the origin of the newly identified proteins, as well as on the conservation of residues relevant for dimerization and DNA binding. Implications of our findings in fundamental areas of biochemistry are illustrated, and perspectives for future research directions are discussed.
Anna Ranaudo, Toshiko Miyake, Haidi Shehi et al.· ACS Omega· 0 citations