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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-HT5AR 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.
Here the authors present the INSERT-seq methodology to investigate the effect of transcribed sequence on processive transcription. The authors find that GC content and splice site sequences are important determinants of elongation potential.
The authors solved structures of nine native band 3-associated complexes from human red blood cell membrane by cryo-EM. Integration of structural and biochemical data supports a model of ankyrin complex assembly during erythropoiesis.
Arrigoni et al. present non-canonical voltage-gated ion channel pore domain (PD) structures demonstrating that the PD is an autonomously folded unit found in diverse proteins and show that PDs can adopt non-canonical forms in full-length channels.
Murray et al. report an approach to identify pathogenic mutations in low-complexity-domain-containing proteins that lead to the formation of amyloid aggregates. Among those characterized are keratin-8 mutations associated with liver disease, linking amyloid aggregation to liver pathology.
Furukawa and colleagues use cryo-EM, molecular dynamics simulations, and electrophysiology to dissect the binding sites of the clinically important channel blockers phencyclidine, ketamine, and memantine to NMDA receptors, providing a blueprint for improved therapeutics.
Circadian clocks both instruct and follow the epigenome. New data reveal that the core-clock PERIOD complex shapes genomic H2A.Z landscapes. H2A.Z, in turn, plays an essential role in rhythm generation by regulating BMAL1 stability.
Cryo-EM, biochemical and cell-based assays reveal strong allosteric autoinhibition of the actin-binding domains of plastins. Physiological tuning of this engagement explains the plastins’ ability to organize actin assemblies of different morphologies.
Cryo-EM structures of human H1-containing tetranucleosome arrays with distinct, physiological nucleosome repeat lengths reveal that nucleosomes assume a zig-zag arrangement and H1 binds to stacked nucleosomes with longer linker DNA.
Here, authors solve cryo-EM structures of the central apparatus of motile cilia and analyze its dynamic conformations to elucidate the mechanism of ciliary beating.