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Here, using mathematical modeling and an in vitro deadenylation system, the authors quantitatively demonstrate the effect of non-adenosines in the poly(A) tail and exemplify how tail sequence regulates mRNA stability.
By investigating key transcription factors in Drosophila, the authors show that pioneering activity is not an intrinsic, binary property. Instead, it is heavily influenced by the level of chromatin occupancy of the transcription factors, which is controlled by multiple protein domains and protein-extrinsic features.
Isaac et al. present mtFiber-seq, a method that measures individual mitochondrial genome packaging at nucleotide resolution. They show that most nucleoids are in an inaccessible state, modulated by the abundance of the DNA-binding protein TFAM.
Using deep mutational scanning, the authors uncover the functional consequence of missense mutations in ARID1B, a subunit of the SWI/SNF chromatin remodeling complex that is frequently mutated in human Coffin–Siris syndrome and in cancer.
Kalienkova et al. use cryo-electron microscopy to capture 3D structures of a neuropeptide-gated DEG/ENaC ion channel in resting and ligand-bound states, detailing the mechanism by which peptides activate these excitatory ion channels.
Here, upon obtaining cryo-EM structures of CRL3KBTBD2 in seven states, the authors propose a model for the activation cycle of CRL3 ligases, including assembly, substrate recruitment, (de)neddylation and CAND1-mediated substrate receptor exchange.
Using cryo-EM, authors reveal the structure and activation mechanism of GPR156, a class C orphan GPCR implicated in sound detection. They find that GPR156 is a transducer for phospholipid signaling and provide insights into the basis for its constitutive activation.
Using cryo-EM, SAXS and HDX–MS, the authors mechanistically delineate dimerization-induced autoinhibition of the HECT-type ligase HACE1 and the selectivity of the active ligase monomer for GTP-bound RAC1.
The authors define a NEDD8-activated cullin-RING E3 poly-ubiquitylation mechanism using chemistry, cryo-EM and rapid kinetics. Near-perfect catalytic efficiency is achieved by an E2 ‘synergy loop’ connecting to the E3, donor and acceptor ubiquitins.
It is unknown how GPR161, an orphan receptor involved in Hedgehog signaling, is activated. This study identifies a sterol that promotes GPR161-driven cAMP signaling but shows that cAMP is dispensable for Hedgehog pathway repression.
Here the authors structurally and functionally characterized a bacterial self-killing CBASS Cap5 immune defense system and demonstrated how it can be leveraged to limit bacterial infections.
Here the authors leverage state-of-the-art quantitative proteomics to provide a comprehensive overview of the human citrullinome. Supporting evidence from peptide microarrays hints at the potential clinical relevance of some of the identified sites.
Here the authors reveal the role of integrin αV and its β-propeller domain in cancer maintenance and identify a novel class of inhibitors that disrupt integrin heterodimer stability via a CRISPR-tiling-instructed computer-aided (CRISPR-TICA) pipeline.
Single-particle cryo-EM, cryo-electron tomography and AlphaFold modeling reveal the structural architecture of the poxvirus core and identify trimers of protein A10 as the key component of the palisade layer.
Here the authors determined structures of the mitochondrial ATP synthase at pH 6, in four distinct conformations. The structures represent intermediates in the reaction cycle of the enzyme and provide insights into its elastic coupling mechanism.
Here the authors visualize the workings of ELOF1 in transcription-coupled DNA repair, showing that ELOF1 repositions repair factors on the surface of DNA damage-stalled RNA polymerase II to facilitate its ubiquitylation by the CRL4CSA E3 ligase and inactivation by UVSSA.
The authors employ cryo-ET to study the structure of the palisade layer of the mature vaccinia virus core in isolation, as well as inside infected cells, revealing that it is composed of A10 protein trimers.
Here, the authors elucidate how sequential activities of opposite-polarity microtubule motors are coordinated on a cargo, by showing how the Tm1 protein inhibits kinesin-1 during delivery of oskar RNA into the Drosophila oocyte by dynein.
A variant predicted to affect chromosome alignment in meiosis associates with intrachromosomal positioning of recombination and increases risk of detectable pregnancy loss by 22%, likely through missegregation of chromosomes.
Structures of complete extracellular receptor assemblies mediated by the pro-inflammatory cytokines IL-12 and IL-23 reveal key commonalities and diverse features, with only IL-12 juxtaposing receptor domains proximal to the cell membrane.