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Amphiphilic protein-polymer conjugates remain largely unexplored due to synthetic protocols being complex. Here the authors explore an oxygen tolerant, photoinduced reversible-deactivated radical polymerization approach, which readily affords quantitative yields within 2 h and thus avoids damage to the secondary structure of the proteins.

Vaccination efficiency in HIV infection is hampered by the low immunogenicity of HIV-1 Env glycoprotein (Env). Here authors optimise the neutralising antibody response to Env by stabilizing the Env trimers in the context of expressing them in a Newcastle Disease Virus-like particle and providing conditions that mimics replicating virus infection.

Access to defined human glycans is crucial for biomedical research. Here, authors report Glycocarriers, a mammalian cell-based method for the sustainable and scalable production of O-, N-glycans, and glycosaminoglycans in various formats including free glycans, glycopeptides, and multimer glycomodules.

Acute myeloid leukemia (AML) arise from mutations of stem and progenitor cells. Here, authors identify a quiescent, label-retaining cell population in AML patient specimens that have tumor-initiation capacity and unique epigenetic and transcriptional properties that can be functionally altered by expression of transcription factors such as JUN.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Microglia mediate the early and selective degeneration of corticostriatal synapses and the development of cognitive deficits in presymptomatic Huntington’s disease via the complement cascade.

A new specific, small-molecule activator of the PI3Kα isoform (UCL-TRO-1938) identified through high-throughput screening can transiently activate PI3K signalling and biological responses in cells and tissues, with potential therapeutic applications in tissue protection and regeneration.

To prevent promiscuous protein degradation, proteasomes are initially assembled as inactive complexes. Their activation is autocatalytic and coupled to assembly. Here the authors uncover key aspects of the autocatalytic activation mechanism.

Crystal structures of DNA methyltransferase M.BceJIV in complex with DNA and sinefungin reveal an unusual mode of DNA binding and methylation, wherein each M.BceJIV monomer contributes to the recognition of two DNA sequences.

The International Union for Conservation of Nature’s Global Ecosystem Typology has been developed to provide a systematic framework for data on all of Earth’s ecosystems in a unified theoretical context to support biodiversity conservation and ecosystem services.

We present near complete cryo-EM structures of the dark and light-activated states of a bacterial phytochrome kinase to reveal how these photoreceptors translate light absorption into conformational changes that impact transmitter kinase cascades.

Woo et al. report new autophagy inhibitors identified through a high-throughput chemical screening using a BRET-based assay and an ATG8 synthetic sensor, that function as safe and effective fungicides against broad fungal pathogens.

Fatty liver disease exacerbates atherosclerosis, but the underlying mechanisms remain unclear. Here, the authors show that D-dopachrome tautomerase (D-DT/MIF-2) acts as an atypical chemokine, promoting both atherosclerosis and hepatic lipid accumulation.

Switchback DNA is a globally left-handed double helical motif formed by two parallel DNA strands. This work presents its unique biophysical, enzymatic, and immunogenic properties and hypothesizes its occurrence in short tandem repeats.

The initiation of prey invasion by the predatory bacterium Bdellovibrio bacteriovorus is governed by the activity of the diguanlylate cyclase DgcB. Here the authors show that the stimulus regulating DgcB activity is a phosphopeptide derived from DgcB itself and present the crystal structures of full-length DgcB and of its empty and peptide-bound sensor domain.

Bacterial autotransporters are folded in a process that entraps segments of their N-terminal passenger domain. Here, Leyton et al. identify glycine-aromatic mortise and tenon motifs that mediate the passenger domain’s translocation to the bacterial cell surface, and show that the motifs are evolutionarily conserved.

Recent studies have shown that energy transfer photoenzymes can be engineered to promote stereocontrolled [2 + 2] cycloadditions; however, existing systems rely on ultraviolet light and display limited photochemical efficiencies. A generation of thioxanthone-containing photoenzymes now harnesses visible light to drive challenging photochemical conversions with high efficiencies and selectivities.

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt βII-spectrin function and disturb cytoskeletal organization and dynamics.

Structures of the human METTL1–WDR4 complex are revealed, providing molecular insights into substrate recognition, modification and catalytic regulation by the N⁷-methylguanosine methyltransferase complex.

π-stacking interactions unique between residues of PUMA and Bcl-xL, which lead to the unfolding of Bcl-xL via an allosteric mechanism, are required to disrupt p53–Bcl-xL interaction and induce apoptosis. This is the first example of regulated protein unfolding for signal transmission.

Employing a candidate gene approach, Mancina et al. identify a genetic variant of the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene that reduces susceptibility to fatty liver disease. Functional studies in vitro and in vivo demonstrate that targeting PSD3 protects against fatty liver disease.

Botulinum neurotoxins (BoNTs), the causative agents of the disease botulism, are potent biological toxins. Here the authors use Designed Ankyrin Repeat Proteins (DARPins) to probe BoNT structure and function: DARPin-F5 that completely blocks SNAP25 substrate cleavage by BoNT/A1 in vitro was identified.

Nuclear import of transcriptional regulators and export of mRNA are essential steps for the manufacture of proteins in the cytoplasm. Here, Rajakylä et al.link these two activities by showing that the mRNA export factor Ddx19 promotes the nuclear import of the transcriptional coactivator MKL1.

The validation of inhibitors targeting PurF, a novel drug target for tuberculosis drug discovery, is described.

Mass spectrometry (MS)-based protein sequencing usually relies on in-solution proteolytic digestion, which is time-consuming and inefficient for certain proteins. Here, the authors achieve full protein sequence coverage in less than 1 ms by subjecting protein-protease mixtures to electrosonic spray ionization-MS.

Mitofusins regulate mitochondrial fusion. Here the authors identify small molecules that activate or inhibit mitofusins’ activity and modulate mitochondrial fusion and functionality. Inhibition of mitochondrial fusion promotes minority MOMP, caspase-3/7 activation, and DNA damage.

Xu, Meng, St-Germain et al. report that S1P in HDL induces a calcium signalling cascade involving E-Syt1 that ultimately promotes the formation of contact sites between the endoplasmic reticulum and the plasma membrane, as well as HDL-derived cholesterol transport.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

CDNF is a clinical trial candidate in Parkinson’s disease but the mechanism of action is not fully understood. Here, the authors use SAXS and NMR techniques to resolve the structure of CDNF in complex with GRP78 and show that this interaction is required for the neuroprotective action of CDNF.

Reported COVID-19 mortality rates have been relatively low in Syria, but there has been concern about overwhelmed health systems. Here, the authors use community mortality indicators and estimate that <3% of COVID-19 deaths in Damascus were reported as of 2 September 2020.

Epsilon toxin (Etx) is a potent pore forming toxin (PFT) produced by Clostridium perfringens. Here authors show the cryo-EM structure of the Etx pore assembled on the membrane of susceptible cells and shed light on pore formation and mutant phenotypes.

Numerical model experiments show that deep valleys cutting across the East African Rift System dry out East Africa by channelling water vapour towards Central Africa, leading to elevated rainfall in the Congo Basin rainforest.

CIGS is a high-resolution dataset comprising chemical perturbation-induced 319,045,108 gene expression events.

An environmentally safe means of mosquito control is the application of Bacillus thuringiensis israelensis, which produces a cocktail of four naturally crystalline proteins exclusively toxic to mosquito. Here the authors report the atomic-resolution structures of Bti Cry11Aa and related Btj Cry11Ba solved de novo through Serial Femtosecond Crystallography on naturally-occurring nanocrystals.

Production of inflammatory mediators by M1-polarized macrophages is thought to rely on suppression of mitochondrial metabolism in favor of glycolysis. Refining this concept, here the authors define metabolic targets of nitric oxide as responsible for the mitochondrial rewiring resulting from polarization.