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Cryo-EM of human PRPS1 shows the nucleotide-synthesizing enzyme assembling into filaments that accommodate active and inhibited conformations. Engineered and disease mutations reveal that filament assembly stabilizes allosteric sites, enhancing catalytic activity.
Tan et al. found that topoisomerase-independent DNA nicking is required for most, if not all, signal-induced acute enhancer activation programs, nucleating formation of a Ku70–HP1γ–Med26 complex required to facilitate transcriptional activation.
Postel et al. have determined a multidomain structure of GR in complex with ligand, DNA and a co-regulator peptide that demonstrates how GR forms a distinct architecture on DNA and how signal transmission can be modulated by the ligand pharmacophore.
Gene transcription initiation is a highly regulated process in which Pol II and general transcription factors assemble into a pre-initiation complex. Structural studies of yeast and human initiation complexes shed light on the role of the first nucleosome flanking gene promoters in controlling the transcription machinery.
Craspase is newly identified type III CRISPR–Cas system with two major components: the nuclease Cas7-11, and the protease TPR-CHAT. Craspases perform a delicate balancing act between nuclease and protease activity to achieve immune tolerance and defense in bacteria, and show promise as highly regulatable genome-editing tools.
Determination of the high-resolution structure of yeast TORC1 allows characterization of the precise interfaces of interaction between inactive TORC1 and TORC1′ polymers and identification of the mode of binding of active EGOC on TORC1.
Comprehensive poly(A)-inclusive RNA isoform sequencing throughout the human oocyte and preimplantation embryo development reveals poly(A)-tail-mediated maternal mRNA remodeling that is essential for human embryo development.
SYCP1 structures are conformationally remodeled by molecular adapter SYCE3 to assemble into the supramolecular synaptonemal complex that mediates chromosome synapsis and facilitates crossover formation in meiosis.
Renner et al. show that HIV-1 concentrates the metabolite IP6 into its virions to catalyze assembly of its iconic conical capsid. Disabling this enrichment mechanism prevents assembly and renders HIV-1 non-infectious.
The Shigella effector OspC3 is activated by binding of host calmodulin to its ADP-riboxanase domain. Structural analyses reveal the mechanisms of caspase-4 substrate recruitment and NAD+-dependent arginine ADP-riboxanation by OspC3.
Moss and colleagues use cryo-EM, brominated lipid probes and molecular dynamics simulations to reveal how membrane curvature stress imposed by membrane-remodeling ESCRT-III proteins alters membrane structure by deforming polyunsaturated lipids.
The sorting and assembly machinery (SAM) mediates mitochondrial β-barrel protein folding and membrane insertion. A cryo-EM structure of the yeast SAM complex bound to an early eukaryotic β-barrel intermediate reveals a multipoint guidance mechanism.
Cryo-EM structures of human DNA-dependent protein kinase in intermediate and active states reveal the molecular mechanism of the allosteric activation of the atypical kinase complex, explaining why it is DNA dependent.
The cryo-EM structures of ESCRT-III CHMP2A and CHMP3 filaments reveal their mode of polymerization and interaction with negatively curved membrane. VPS4 constricts and cleaves the ESCRT-III CHMP2A–CHMP3 membrane tubes, thus acting as a minimal membrane fission machinery.
