Articles

Elango et al. identify a new class of substrates on which the Fanconi anemia SLX4–XPF nuclease operates to mediate homologous recombination at DNA–protein replication fork barriers and promote cellular tolerance of DNA–protein cross-links.

An endogenous proteasome inhibitor was identified 30 years ago, but its mechanism remained unclear. Rawson et al. show that this inhibitor is present within the interior of the proteasome, where it simultaneously inhibits all six active sites.

Functional assays and cryo-EM structures show that ubiquitin binding and a cofactor drive protein quality-control client selection by the hybrid E2/E3 enzyme UBE2O.

Here, the authors find that histone demethylase Epe1-mediated stress resistance is regulated by proteasome-dependent truncation, allowing heterochromatin to reprogram gene expression that confers antifungal resistance to some fission yeast cells in the population.

Cryo-EM, X-ray crystallography and crosslinking mass spectrometry are harnessed to solve the structure of the full-length Rho-GEF P-Rex1, uncovering a two-layered mechanism of autoinhibition released upon Gβγ and PI(3,4,5)P3 binding.

This work reveals the structural and biochemical basis for phosphorylation-dependent day/night signaling by KaiC in the cyanobacterial circadian clock.

Clemons and colleagues identify a guided entry of tail-anchored proteins (GET) pathway in the pathogen Giardia intestinalis and characterize it structurally, revealing several previously unknown structures of the central protein Get3. The work resolves some important open questions and results in a comprehensive model for the insertion of tail-anchored membrane proteins.

Cryo-EM structures of human erythrocyte ankyrin-1 complex offer insights into the architecture of the RBC membrane and show how ankyrins can simultaneously recruit different membrane proteins to enable functional organization of membrane transport processes.

Single-molecule experiments reveal that condensin-induced DNA looping is stimulated by positive supercoils, and condensin preferentially binds near the tips of supercoiled plectonemes; upon loop extrusion, condensin collects nearby DNA plectonemes into a supercoiled loop.

Here authors visualize dynamics GAGA pioneer factor (GAF) association with chromatin in vivo in Drosophila hemocytes. The characterization of GAF kinetics provides a temporal mechanism for maintenance of open chromatin for transcriptional responses to homeostatic, environmental and developmental signals.

This comprehensive study of the most enigmatic serotonin receptor 5-HT_5AR includes lots of pharmacological investigations, inactive and active state structures with antagonist, partial agonist and full agonists. Also, a highly potent and selective antagonist was developed.

Multiple cryo-EM structures of human glycogen synthase reveal the basis of inhibition by phosphorylation and allosteric activation by glucose-6-phosphate.

Cryo-EM analysis of the human apelin receptor activated by either the endogenous peptide ligand or a potent synthetic small-molecule agonist reveals a mixture of homodimer and monomer organizations shedding light on a versatile regulation mechanism.

Atomic-resolution structures of an important antifungal target, chitin synthase 2, from a pathogenic fungus, Candida albicans, reveal a unique domain-swapped dimeric assembly and provide insights into the mechanism of antifungal action.

This study uncovers a new mechanism linking oxidative stress to telomere-driven senescence. A common oxidative lesion at telomeres causes rapid premature cellular aging by inducing telomere fragility, rather than telomere shortening.

Functional and structural characterization of rhodopsin-bestrophin fusion proteins from marine algae unveils the existence of giant light-sensitive anion channels with unusual biophysical properties.

Major facilitator superfamily protein MFSD2A takes essential omega-3 fatty acids into the brain, and is the receptor of SYNC2 membrane fusogen in placenta. A cryo-EM structure of the human MFSD2A–SYNC2 complex reveals key aspects of MFSD2A transport and receptor mechanisms.

Here the authors build different regulatory landscapes in an inactive chromatin environment and observe that enhancers can both carry out their classic role of stimulating transcription initiation and elongation at target gene promoters and recruit cohesin to create contact domains, engage CTCF sites and activate distant genes.

Here, authors use targeted degradation and Hi-C in eukaryotic cells to show that acetylation of the cohesin subunit Smc3 stops loop extrusion during DNA replication by recruiting Pds5, also required for sister chromatid cohesion, and by preventing Scc2-dependent loop expansion.

Here, the authors use gene editing combined with Hi-C to show that cohesin acetylation restricts the length of chromatin loops through enhanced binding of cohesin to PDS5A.