Browse Articles

Here, the authors discuss the various roles of the HUSH transcriptional silencing complex and its dysregulation in disease.

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 concluding statement of Watson and Crick’s historic paper on the structure of DNA¹ enshrines a key tenet of molecular mechanistic cell biology: “… the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material”. Function — heredity in this case — is embedded in the redundant sequence information of the two strands of DNA. Although not always expressed as blatantly, the intimate dependence of cellular function on the mechanical level of macromolecules is inspirational. The devil is in the structural detail, and the painstaking quest for the correct details and their returns in the form of reliable knowledge knows no shortcuts.

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 Escherichia coli, 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-HT_3AR 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.