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Commentary

The quest for new robust bacterial monoamine oxidases

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Microbial enzymes are versatile, cost-effective, and sustainable tools, making them a preferred choice for enzymatic processes. Santema and colleagues harnessed AlphaFold, a cutting-edge structure prediction tool, to discover new thermophilic monoamine oxidases (MAO) that could be relevant for drug development and use in biotechnology fields. This bacterial enzyme, paired with recent advancements in enzyme engineering, has the potential to meet the biotech sector's need for customized enzymes.

Comment on: https://doi.org/10.1111/febs.16973

Commentary

NTNH protein: more than a bodyguard for botulinum neurotoxins

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Nontoxic nonhemagglutinin (NTNH) is a protein co-secreted with botulinum neurotoxin (BoNT) by bacteria. A new cryo-EM structure of a BoNT-like toxin from Weissella oryzae (BoNT/Wo) in complex with its NTNH suggests that NTNH/Wo plays a conserved role as canonical NTNHs in stabilizing and protecting BoNTs. Furthermore, NTNH/Wo displays some unique structural features including two extra Big domains, suggesting NTNH/Wo may be involved in host targeting and play additional roles during BoNT intoxication.

Comment on: https://doi.org/10.1111/febs.16964.

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State‐of‐the‐Art Review
Open access

Too big not to fail: emerging evidence for size‐induced senescence

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Senescence is a permanent state of cell cycle arrest and plays an important role in development, aging, and cancer biology. Although senescent cells are known to be larger than proliferative cells, recent research has revealed that increased cell size is not only a consequence but also a cause of permanent cell cycle exit. This review illustrates how excess cell size alters normal cell physiology and contributes to senescence induction.

Viewpoint
Open access

Tumor immune evasion: insights from CRISPR screens and future directions

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Despite the clinical success of cancer immunotherapies including immune checkpoint blockade and adoptive cellular therapies, many patients do not respond or ultimately relapse. We discuss the use of CRISPR/Cas-based approaches to identify mechanisms of tumor immune evasion and avenues to sensitize cancers to destruction by the immune system. We provide a perspective on screening approaches and review the further development of technologies to improve such approaches and discovery capability.

Original Article
Open access

A poly-proline II helix in YadA from Yersinia enterocolitica serotype O:9 facilitates heparin binding through electrostatic interactions

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YadAO:9, the major adhesin of Yersinia enterocolitica serotype O:9, harbors an N-terminal poly-proline II helix that facilitates heparin binding. Binding is based on electrostatic interactions between basic residues within the YadAO:9 motif and sulfate groups of heparin. This interaction is important for host cell binding: YadAO:9-mediated adhesion to cells deficient in heparan sulfate production is significantly reduced.

Original Article

The influence of a copper efflux pump in Histoplasma capsulatum virulence

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Histoplasma capsulatum elevates Crp1 expression in the presence of copper in vitro or in macrophage infection. Copper chelation hampered macrophage ability to control the fungus, while fungal burden decreases in copper-treated immune cells. ATP7a silencing (phagosome copper pump) also caused increased fungal burden. H. capsulatum CRP1-knockdown strains attenuated virulence. These data show that copper increase is a strategy for phagocytes to control H. capsulatum, and Crp1 is responsible for H. capsulatum virulence.

Original Article

Cytosolic phospholipase A2 regulates lipid homeostasis under osmotic stress through PPARγ

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Hyperosmolality induces cPLA2 expression and translocation from the cytosol to intracellular membranes. Once activated, cPLA2 releases arachidonic acid (AA) from membrane glycerophospholipids. Free AA can be converted to prostaglandins (PG) through the COX2 enzyme or can activate the PPARγ nuclear receptor, which in turn induces triglyceride (TG) synthesis and accumulation in lipid droplets. TG synthesis contributes to osmoprotection of renal epithelial cells under osmotic stress.

Original Article
Open access

Comparative analysis of PDZ‐binding motifs in the diacylglycerol kinase family

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Diacylglycerol kinases (DGKs) are crucial proteins that regulate the levels of key signaling lipids. Many of these enzymes contain a C-terminal peptide region that sequentially corresponds to a PDZ domain recognition motif (PBM). In this study, the authors comprehensively studied the PDZ-PBM interactome of these enzymes using different interactomic approaches, supported by evolutionary conservation analyses. They were able to reveal functional differences between PBMs of different types of DGKs.

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