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Kuhm et al. reveal how human guanylate-binding protein 1 (GBP1) dimers self-associate to coat bacterial pathogens and uncover a guanosine triphosphate hydrolase-dependent membrane-remodeling activity of GBP1 that is crucial for intracellular immunity
An understudied subset of NOD-like receptors are involved in the reproductive system, and their dysfunction can cause infertility. The recently obtained structures of the core subcortical maternal complex assembled around one of them, NLRP5, provide important insight into this building block of early embryo cytoplasmic lattices.
On the basis of the assembly mechanism and structures of the human subcortical maternal complex, the authors provide a strategy for the diagnosis of reproductive disorders and the discovery of new infertility-associated SCMC variants.
The authors present structures of endosomal sorting complexes required for transport III family member vesicle-inducing protein in plastids 1, ranging from helical assemblies and stacked rings to flat carpets, providing insights into transitions dependent on membrane tubulation and curvature needed for forming different architectures involved in membrane remodeling.
Live-cell single-molecule imaging of pioneer transcription factors revealed a ‘confined target search’ mechanism where they alternate between fast free diffusion in the nucleus and slower confined diffusion within compacted chromatin domains, leading to efficient pioneering on closed targets.
This study presents the cryo-electron microscopy structure of Fanzor2, showcasing its unique structural elements and nucleic acid interaction sites. A comparison to TnpB-related RNA-guided endonucleases highlights divergent evolutionary paths.
Here the authors experimentally describe the secondary structure of the NORAD long noncoding RNA in human cells. NORAD’s modular structure and specific structural elements allow it to efficiently antagonize the Pumilio RNA-binding proteins.
Hyaluronan (HA) is an essential glycosaminoglycan. Here, the authors provide mechanistic insights into how HA synthase synthesizes HA and creates a membrane-spanning secretion channel, as well as how channel-lining residues modulate the HA length distribution.
Here, cryo-electron microscopy structures reveal how the chemokine receptor CXCR4 oligomerizes and how it is regulated by its physiological ligand CXCL12, the small-molecule drug AMD3100 and the monoclonal antibody REGN7663.
Here, the authors unveiled a ‘super-silencer’ and its mechanisms of action. They revealed that a combined treatment of an enhancer of zeste homolog 2 inhibitor and a repressor element 1-silencing transcription factor inhibitor can disrupt super-silencers, potentially leading to cancer ablation.
High-resolution structures of DNA-bound multiprotein Spo11 complexes, the DNA-cleaving ensembles that initiate meiotic recombination, elucidate the structural basis of its DNA-binding specificity and explain recombination initiation patterns in vivo.
The authors uncover the roles and regulations of DNA polymerase κ (Polκ) during DNA damage bypass. In addition to a catalytic function across minor groove DNA lesions, Polκ stimulates Polζ-mediated extension past various DNA lesions.
Cryo-electron microscopy reveals the mechanism of human translation initiation from codon scanning to subunit joining. The structures show the roles of the Kozak sequence, GTP hydrolysis by eukaryotic initiation factor 2 (eIF2) and eIF5B in 48S remodeling, as well as that of eIF3 in the control of 60S docking.
Here, the authors show that bromodomain-containing protein 4 is recruited to the MYC enhancer by Mediator and activates transcription through elongation factors independently of bromodomains. This mechanism contributes to bromodomain and extraterminal domain inhibitor resistance in estrogen receptor-positive breast cancer.
Exocytosis of secretory vesicles is required for cellular growth, cellular division and cell–cell communication. Lee et al. reveal that the exocyst tethering complex has stimulatory roles in exocytic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly and SNARE-mediated vesicle fusion.
Using cryo-electron tomography of human T cell leukemia virus type 1 virus-like particles, the authors reveal that the immature Gag lattice is stabilized by the capsid N-terminal domain in contrast to other retroviruses that use the C-terminal domain.
Germline small RNAs in plants and mammals are marked by pseudouridine. In plants, Exportin-t is required for pseudouridylation, transport and localization of small RNAs in pollen, as well as for epigenetic inheritance in the form the triploid block.
Anti-NMDA receptor encephalitis is the most common autoimmune encephalitis. Michalski et al. reveal epitope diversity, conformational changes and functional impacts of the autoantibodies using cryo-EM and electrophysiology.