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Here, the authors provide a comprehensive atlas of stress-responsive phosphorylation in yeast. Their unprecedentedly deep datasets allow them to showcase shared and divergent signaling events between stressors and to unveil functional organization principles.
The Review provides an overview of ion-channel insecticide targets, with a focus on their mechanisms of action, and offers a perspective for structure-based development of insecticides.
Here the authors report the structures of OAT1, a drug transporter implicated in transporter-mediated drug interactions, unveiling the mechanism of its polyspecific substrate binding.
Here, using single-molecule experiments, the authors show that SpCas9 responds to shifted PAMs by inducing overhanging DNA ends. Such shift-PAM targeting is enhanced by physiological levels of DNA supercoiling and in turn promotes dissociation of the complex after catalysis.
The targeting and modulation of G-protein-coupled receptors (GPCRs) has immense therapeutic potential. A study in Nature now reports on the successful targeting of intracellular allosteric sites that effectively bias GPCR signaling, which has opened new opportunities to develop safer therapeutic agents.
Using structural and functional analysis, Li et al. reveal the architecture of the Rpd3S histone deacetylase complex and mechanism of its chromatin targeting and deacetylation.
This study shows that CRISPRi mediates precise transcriptional pausing, which can be followed by transcription termination. The pausing effect is asymmetric, only being induced when dCas9-bound guide RNA anneals to the non-template DNA strand.
The release of inorganic phosphate (Pi) from actin marks old actin filaments for disassembly. By combining cryo-electron microscopy (cryo-EM) with in vitro reconstitution and molecular dynamics simulations, we show how actin filaments release Pi through a ‘molecular backdoor’ and demonstrate that this arrangement is distorted in a disease-linked actin variant.
The authors present the full-length dimeric TRIM72 E3 ubiquitin ligase and the architecture of its high-order assembly bound to a phosphatidylserine-enriched membrane, providing insights into its role in membrane repair and ubiquitylation.
This study describes an approach to segment and extract key biophysical parameters from live-cell three-dimensional single-molecule imaging trajectories. The authors use this approach to study how NuRD assembles on chromatin and how it regulates enhancer dynamics.
Here, the authors constructed a deep-learning approach to design closed repeat proteins with central binding pockets—a step towards designing proteins to specifically bind small molecules.
The authors solved the cryo-EM structure of Myomaker, essential for myoblast fusion, and showed that it adopts a GPCR-like fold. They pinpointed the role of the dimeric interface and lipid-binding sites for fusion, and proposed a mechanism that may be conserved between species.
Release of inorganic phosphate (Pi) from actin marks older actin filaments for disassembly. Here, the authors show how Pi exits the F-actin interior through a ‘molecular backdoor’. The backdoor arrangement is distorted in a disease-linked actin variant.
Here, the authors show that PDHE1α accumulates at DNA double-strand breaks, in a PARylation-dependent manner, where it locally supplies acetyl-CoA for histone acetylation. These events facilitate remodeling of the chromatin landscape and efficient repair.
Here, using cryogenic electron microscopy and cryoDRGN, the authors delineate how the anaphase-promoting complex/cyclosome is reconfigurated to interact with its cognate E2s and thus polyubiquitinate its target. Unexpectedly, multiple ubiquitin moieties are shown to interact with the anaphase-promoting complex/cyclosome machinery, including its activator Cdh1.
Here, the authors unveil the intrinsic ability of the C terminus of SSX, as part of different oncogenic fusions, to determine fusion occupancy independent of the BAF complex by both recognizing and stimulating histone H2AK119 monoubiquitylation by PRC1.1.
Here the authors show that the m6A modification on mRNAs mediates their length-dependent enrichment in stress granules, and that mRNAs with longer exons—which usually harbor more m6A sites—are preferentially enriched in the granules.
By obtaining structural snapshots of the catalytic cycle of NADH:quinone oxidoreductase from Vibrio cholerae, the authors uncover its mechanism. They show how electrons are shuttled and determine the importance of the [2Fe-2S] cluster in the movement of the electron transfer switch.
Here, using cryo-EM, the authors show how Cas1–Cas2/3 and integration host factor, by means of a U-shaped bend that traps the invading DNA and a loop that positions it for the integrase, regulate integration of foreign DNA into the first repeat of the CRISPR array.