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Here the authors report that TFAP2C and NR5A2, two TF lineage regulators, activate both inner cell mass and trophectoderm programs in totipotent mouse embryos, leading to ‘bipotency activation’ to initiate the first cell-fate specification.
Using a combination of bioinformatics, biochemistry, genetics, genomics and cell-based approaches, this study shows that the H3–H4 binding capacity of the histone chaperone SPT2 is required to preserve chromatin structure and function in Metazoa.
In this study, Asami et al. present the cryo-EM structure of the complex between hepatitis B virus protein and its host entry receptor NTCP, which provide a blueprint for the rational design of anti-HBV drugs targeting virus entry.
MRP4 is an ATP-binding cassette transporter that transports prostanoids, a group of signaling molecules. The authors use cryo-EM to visualize the transport cycle and characterize its substrate selectivity.
Here, the authors structurally characterize two sequential complexes leading to prespliceosome assembly, providing insights into the mechanism of branch site proofreading in the human spliceosome.
Using targeted proteomics, the authors reveal concurrent mitotic binding of nuclear receptors, a super-family of transcription factors that emerge as recurrent mitotic bookmarking factors, promoting the reactivation of the pluripotency network in embryonic stem cells.
In intracellular trafficking, transport vesicles deliver cargo via membrane fusion. The fusion machinery includes both tethering factors and SNAREs. The cryo-electron microscopy structure of a tether–SNARE complex reveals the basis for their collaboration.
The ubiquitin E3 ligase UBR4 is a key component of the ubiquitin N-degron pathway, but the domain that catalyzes ubiquitin transfer remains unknown. Here the authors identify its unorthodox E3 module and characterize its structure and ubiquitin transfer mechanism.
Here, the authors solve structures of human DHHC9 with accessory protein GCP16 and their yeast counterpart Erf2–Erf4. The work provides insights into regulation of Ras proteins by palmitoylation, showing that accessory proteins are not involved in catalysis.
Here, the authors provide mechanistic insights into how decitabine-induced DNA hypomethylation can potentially overcome endocrine resistance in ER+ breast cancer, by targeting the 3D epigenome to resolve gene deregulation and suppress tumor growth.
The authors present the structures of chemokine receptor CXCR3 complexed with agonists CXCL11, PS372424 and VUF11222 and antagonist SCH546738, providing a basis for the ligand recognition and activation mechanism of CXCR3.
Autophagy is essential for cellular homeostasis which decreases with age. Here, the authors identify aging-induced reduction of DHHC5-mediated beclin 1 palmitoylation as an underlying mechanism by which aging induces autophagy decline in the brain.
Here, using proteomics, next-generation sequencing, biochemistry and cryo-EM, the authors delineate the role of CedA as an unconventional transcription factor in Escherichiacoli, which protects from different stressors, including antibiotics, by regulating the transcriptional landscape.
Here, by sub-kb Hi-C and chromosome engineering, the authors visualize bacterial transcriptional units, showing that they form transcription-induced domains. Transcription-induced domains enforce constraints on nearby sequences, affecting their localization and dynamics.
Here authors developed a computational method to design complicated all-α structures using typical helix–loop–helix motifs and canonical α-helices, and demonstrated the ability to create complicated all-α proteins.
Authors provide analysis of starch-binding protein Sas6, from Ruminococcus bromii, a bacterium that degrades resistant starch granules in the human gut, and demonstrate how carbohydrate-binding modules recognize different moieties within starch.
Drugs with partial activity at the serotonin 3 receptors (5-HT3R) are suited to normalize serotonin response in treating irritable bowel syndrome. Felt et al. demonstrate the mechanism of partial agonism in 5-HT3AR using cryo-EM.
Here the authors delineate how pioneer factor Pax7 promotes chromatin relaxation, by initially mediating the deposition of activating marks and at times the removal of repressive chromatin modifications, subsequently enabling the recruitment of chromatin remodelers to displace nucleosomes and activate enhancers.
Here the authors show that, when phosphorylated at Tyr34, THEMIS behaves as an allosteric activator to phosphatase SHP1, ensuring appropriate negative regulation of T cell antigen receptor signaling and thus assisting in T cell maturation and expansion.
Here, the authors use a massively parallel reporter assay RNA polymerase II massively systematic transcript end readout, to quantify factors that influence transcriptional start site selection in the genome of Saccharomyces cerevisiae to reveal patterns of dependence on DNA sequence, RNA polymerase II activity and nucleoside triphosphate abundance.