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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.
The NLRC4 inflammasome, vital for immune defense, responds to infections and inflammation. Here the authors reveal the role of Bacillusthailandensis type III secretion system needle protein in activating NLRC4 complex through structural insights.
By probing the epigenome in differentiating DNA methylation-free murine ESCs, the authors uncover a subset of germline and neural enhancers sensitive to DNA methylation. Failure to decommission these elements leads to biased adoption of these fates over other lineages.
How do intrinsically disordered proteins behave inside the cell? Moses et al. show that these flexible proteins contain structural preferences inside cells, and that these preferences can change with the composition of the intracellular environment.
Here, the authors demonstrate that CAND1 increases the dissociation rate of CRL2s, thus exerting an inhibitory effect, which in turn endows CRL2s with a selectivity for different targets based on their affinity for CRL2, thereby pacing protein degradation.
Here, using cryo-EM, in vitro and cellular assays, the authors elucidate how SS18–SSX1, via an unorthodox manner of selectively recognizing ubiquitylated nucleosomes, hijacks the BAF1 complex to Polycomb-repressed regions in synovial carcinoma.
Here, using cryo-EM, the authors delineate how the chromatin remodeling complex of ISWIa binds dinucleosomes. Their findings showcase synergistic interactions between ISWIa subumnits and neighboring nucleosomes, thus exemplifying the nucleosome spacing activity of ISWIa.
Using structural, biochemical, and functional assays, the authors demonstrate that the E3 ligase KLHDC2, via newly developed small-molecule ligands, can be co-opted to target critical targets for degradation.
Here the authors show that TET dioxygenases, the erasers of DNA methylation, use a self-limiting mechanism via their LCD domain to ensure adaptable methylome status and protect the genome from excessive oxidative methylation.