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Here, the authors show that the canonical BRG/BRM-associated factor (SWI/SNF) chromatin remodeler generates subnucleosomes containing 50–80 bp of DNA associated with the four core histones. These hemisome-like particles interact with OCT4 to expand its binding domain at enhancers.
The authors uncover a Père David’s deer-like design for long noncoding RNAs such as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which partially mimics the transfer RNA (tRNA) structure to recruit select tRNA processing enzymes for maturation and to create novel regulatory RNAs such as the MALAT1-associated small cytoplasmic RNA.
Cryo-EM structures of the human mitochondrial chaperone Hsp60 reveal alternating apical domain conformations that enable simultaneous client and co-chaperone interactions. These results provide a structural mechanism for efficient client capture and chaperone cycling.
This study uses single-base tiled screens, bioinformatics, comprehensive mutagenesis and proteomics to provide a high-resolution view of RNA silencing with PspCas13b. It reveals design principles for potent silencing without collateral effects.
The authors use cryo-electron microscopy and biochemistry to reveal how 3-methylcytosine (m3C) methyltransferases bind tRNA. They also find that the human m3C methyltransferase METTL6 forms a tRNA-dependent complex with seryl-tRNA synthetase to methylate target tRNAs efficiently.
The H2AK119Ub is inversely regulated by nucleosomal deubiquitinase. Here the authors report the cryo-EM structure of single-subunit USP16 bound to H2AK119Ub nucleosome, unveiling a fundamentally distinct mode of H2AK119Ub deubiquitination compared to multi-subunit PR-DUB.
Mitophagy is an important quality control pathway. Here, the authors identify the mechanisms enabling the TBK1 adaptors NAP1 and SINTBAD to prevent hyperactivation of PINK1/Parkin mitophagy while promoting the pathway once set in motion.
What is the role of disorder in non-homologous end-joining proteins? The authors use nuclear magnetic resonance to reveal that disordered regions mediate a network of multivalent interactions, promoting biomolecular condensation that accelerates DNA ligation kinetics.
The synaptic vesicle protein 2 family are essential membrane proteins found in the brain that bind synaptotagmin and are targeted by anti-seizure medications. Structures reveal common features found in transport proteins, and the basis of ligand binding and selectivity.
Here, using nuclear magnetic resonance spectroscopy, the authors delineate how the molecular chaperone Hsp90, in its open state, uses its two middle domains to synergistically capture a disordered client in a highly dynamic manner, forming a bipartite complex.
Cryo-EM structures covering full-length yeast Smc5/6 in three states and the accompanying mutagenesis data reveal multiple new structural and functional features of this unique SMC complex.
Cryo-EM structures of the human clamp unloader ATAD5-RFC bound to the sliding clamp PCNA reveal two unique locking loops and one chamber plug that prevent DNA from entering the ATAD5-RFC and explain why ATAD5-RFC is exclusively a PCNA unloader.
The authors identified PRDX6 as a novel selenoprotein synthesis factor performing an iron-induced ferroptosis screen. They reveal that PRDX6 greatly facilitates selenium utilization for selenoprotein synthesis by acting as a selenide carrier protein.
Using molecular dynamics simulations and functional assays, authors track the structural changes in heterotrimeric G proteins in response to receptor coupling that lead to the ejection of GDP, the rate-limiting step during G-protein activation.
The cryo-EM structure of the full 80S human ribosome is presented at 1.9 Å resolution. Numerous new chemical modifications are resolved, resulting in over 230 annotated sites cross-validated by mass spectometry. Ions and water molecules are seen to stabilize the RNA architecture.
Using naive human embryonic stem cells as a model for early embryogenesis, the authors report that the XIST (X-inactive specific transcript) long noncoding RNA recruits repressive histone marks and attenuates X chromosome expression before the establishment of X chromosome inactivation.
Here the authors elucidate how epigenetic regulation influences the regulatory impact of transposable elements in the human genome using cellular models of the neurodegenerative disease XDP, which is caused by an SVA insertion at the TAF1 locus.
Using cryo-electron microscopy, the authors reveal the mechanism by which perampanel-like molecules inhibit AMPA receptors. They show that the inhibitors decouple the ligand-binding domain from the ion channel after neurotransmitter binding and outcompete positive modulators.
Autophagy degrades cellular waste by engulfing it in phagophore membranes and delivering it to lysosomes for degradation. Here Mohan and colleagues identified a type of membrane coat that assembles on phagophores to guide their expansion.