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Structural and biochemical analyses identify the ZZ domain of p300 as a novel histone H3–binding module that promotes p300 chromatin association and is required for selective acetylation of H3K18 and H3K27 in human cells.
The interactions between HIV-1 Env and host cell receptors CD4 and CCR5 or CXCR4 are examined using direct stochastic optical reconstruction microscopy and fluorescence fluctuation spectroscopy imaging, revealing a dynamic three-step process leading to formation of the pre-fusion complex.
Cryo-EM analyses of human LRRC8A show a homohexameric assembly that can adopt two conformations, compact or relaxed, indicating rigid-body motions that might be involved in channel gating.
A new approach to map nucleosome array regularity and spacing reveals modulation of array regularity and nucleosome repeat length depending on functional chromatin states.
Four crystal structures of the human serotonin receptor 5-HT2BR in complex with chemically and pharmacologically diverse drugs elucidate the structural bases for receptor activation, agonist-mediated biased signaling and β-arrestin2 translocation.
In situ Hi-C and other genome-wide and imaging analyses in different mouse embryonic cell types reveal that the noncanonical SMC protein Smchd1 regulates long-range chromatin interactions and the developmental silencing of Hox genes.
The cryo-electron microscopy structures of the mouse TRPV3 channel, in the closed apo and agonist-bound open conformations, provide insights into the mechanism of activation.
In vitro assays and high-resolution microscopy show that Pol II CTD undergoes length-dependent liquid phase separation and controls Pol II clustering and mobility in human cells.
A screen for C. elegans antiviral-defense genes identifies a homolog of the mammalian TUT4(7) terminal uridylyltransferase genes and leads to the discovery of 3′-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.
A set of GFP fusions with as few as 12 residues appended to the C terminus is shown to assemble into filaments in E. coli. Crystal structures reveal a mechanism termed ‘runaway domain coupling’ and illustrate how protein filament formation can evolve.
Time-resolved X-ray crystal structures of RNA hydrolysis by RNase H1 reveal that cations in addition to the two canonical Mg2+ ions position the reactants in the active site and enable catalysis.
Cell-based and in vitro analyses reveal that BRD4 functionally associates with eRNAs and that BRD4 bromodomains, through eRNA interactions, promote BRD4 binding at mutant p53-targeted enhancers to augment enhancer activation and tumor promoting gene expression.
The mechanism underlying CCG-repeat expansions in patients with fragile X premutation is not well understood. Using a new experimental system in mammalian cells, a study in this issue reports that break-induced replication has a role in CGG-repeat instability.
A series of new cryo-EM structures reveals a surprising twist in how the RAG complex initiates V(D)J recombination. The initial complex with substrate DNA adopts two conformations: in one, the DNA is relatively undistorted but the scissile phosphate is far from the active site, and in the other the DNA is partially melted and unwound by half a turn, which allows the scissile phosphate to dock into the active site. Similar pre-catalysis DNA melting may occur with other DDE recombinases, for which equivalent complexes with uncleaved substrate DNA are not yet available.
The effects of RNA secondary structure on translation have been well recognized; however, the global interplay between both in a dynamic cellular system is poorly understood. Beaudoin, Giraldez and colleagues have analyzed RNA structure dynamics during zebrafish embryonic development and have found that the ribosome unzips mRNA secondary structure during translation, thus leading to a global decrease of structure in highly translated transcripts. Furthermore, the authors establish RNA structure in the 3′ untranslated regions of mRNAs as a major regulator of transcript stability in this context.
A new system to analyze the instability of fragile X (CGG)n repeats in mammalian cells suggests that long repeats cause replication fork stalling, resulting in repeat length changes and mutation at a distance via break-induced replication.
The cryo-EM structure of human αvβ8 integrin in the extended-closed conformation shows the headpiece rotating about a flexible αv-knee, suggesting a ligand surveillance mechanism for integrins.
The mitochondrial fission dynamin (Dnm1) from an algae is captured in a closed conformation, with the GTPase domain compacted against the stalk. This work indicates that formation of the closed conformation may contribute to membrane fission.
Characterization of mRNA structure during the zebrafish maternal-to-zygotic transition identifies the ribosome as a major RNA structure remodeler in vivo and reveals that structural dynamics can affect gene expression, partly by modulating miRNA activity.
