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An integrative approach has now enabled elucidation of the complete biosynthetic pathway of a prominent saponin adjuvant. Reconstruction of the whole biosynthetic pathway in a heterologous host provides new perspectives for the biotechnological supply of this immunostimulant.
A method called MEDUSA was developed for identifying death regulatory genes in chemo-genetic profiling data, which enables characterization of a previously unappreciated mechanism of death induced by DNA damage in p53-deficient cells.
The study demonstrates that specific recognition and custom binding geometries can be computationally encoded between protein spans within lipids through designing synthetic transmembrane proteins to functionally regulate a target cytokine receptor.
Reprogramming of the genetic code allows the synthesis of proteins using new building blocks, thus opening the door to the development of a wider variety of medicines and biocatalysts; however, it is currently limited to α-amino acids. A new study has now reported the incorporation of β-linked and α,α-disubstituted monomers into a ribosome-synthesized protein.
NMR and Raman spectroscopies pinpoint the role of the protein droplet surface and RNA in the liquid droplet maturation mechanism of the FUS protein. A crust-like β-sheet structure is formed on the surface of FUS droplets during aging.
The rate of ATP production and the total mass of enzymes were quantified for both glycolysis and mitochondrial respiration to determine the proteome efficiency of these pathways. Per unit of enzyme mass, mitochondrial respiration generates energy faster than glycolysis and is thus more proteome efficient. Despite being less proteome efficient, constitutive glycolysis comes with the benefit of rendering cells robust to hypoxia.
AlphaFold is a breakthrough in protein structure prediction, but limitations in its application to computation- and structure-guided drug discovery remain. As with structure prediction, public-domain data and benchmarking initiatives will be essential to advance the field of computational drug design.
Kir4.1 potassium channels expressed in astroglial cells critically regulate extracellular potassium concentration in the brain. A new study reports that blocking the flow of potassium ions into astrocytes by inhibiting Kir4.1 induces rapid-onset antidepressive effects in rodents.
Labeling of endogenous proteins with chemical probes is highly desirable for life science studies. The combination of RNA base editing and site-specific incorporation of non-canonical amino acids allows the introduction of small chemical tags into endogenous proteins in living cells.
Yang et al. reported the development of nongenetically engineered artificial mechanoreceptors capable of reprogramming non-mechanoresponsive receptors to sense user-defined force cues, enabling de novo-designed mechanotransduction.
Aerobic glycolysis is a hallmark of fast-growing cells, but it is unclear whether glycolysis was selected for its speed. Glycolysis produces ATP slower than respiration (per protein mass) and is beneficial for rendering cells robust to hypoxia.
Inhibitors of KRAS G12C have shown that directly targeting RAS is possible, but G12C is only one of many RAS driver mutations. Covalent targeting of another major variant, G12D, raises hope for treating other groups of patients with KRAS-mutant tumors.
Development of a malolactone electrophile that contains sufficient ring strain to counteract the weak nucleophilicity of aspartate enables covalent targeting of K-Ras-G12D, which is commonly found in pancreatic cancers.
Chemically reactive metabolites such as formaldehyde are often toxic and are proposed to react promiscuously with biomolecules. New work shows that some reactive sites on proteins are uniquely sensitive to formaldehyde, leading to functionally important regulation of protein and cell functions.
A proteome-wide thermal profiling study of osmolyte action on E. coli and human proteins within the cellular milieu reveals mechanisms of protein thermal stabilization by osmolytes and in situ behavior of intrinsically disordered proteins.
Structural, functional and computational studies uncover the molecular details of antiviral drug recognition and membrane translocation by a concentrative nucleoside transporter.
This Review provides an overview of different RNA base editing technologies, including the RNA-targeting platforms and modification effectors, with a focus on the emerging programmable RNA base editors and their potential in correcting pathological mutations.
Adipose triglyceride lipase (ATGL), an enzyme in fatty acid metabolism, was identified as a negative regulator of the noncanonical inflammasome. ATGL binds to lipopolysaccharide and catalyzes the hydrolysis of fatty acid side chains blocking inflammasome activation.
A chemoproteomic method was developed that enables the global discovery of metal-binding proteins (MBPs) in proteomes, where the thermal stability of MBPs is perturbed by metal chelators. This tool, called METAL-TPP, is used to discover MBP candidates in the human proteome and provides a valuable method for functional annotation of MBPs in cell biology.