Nature Structural & Molecular Biology, Published online: 05 December 2025; doi:10.1038/s41594-025-01717-zRiechmann et al. uncover structural features governing ubiquitin transfer from ubiquitin-activating E1 enzymes UBA1 and UBA6 to specific E2 ubiquitin-conjugating enzymes, revealing a hierarchy of E2 activity with cognate E1s.

Nature Structural & Molecular Biology, Published online: 05 December 2025; doi:10.1038/s41594-025-01717-zRiechmann et al. uncover structural features governing ubiquitin transfer from ubiquitin-activating E1 enzymes UBA1 and UBA6 to specific E2 ubiquitin-conjugating enzymes, revealing a hierarchy of E2 activity with cognate E1s.

Nature Structural & Molecular Biology, Published online: 03 December 2025; doi:10.1038/s41594-025-01730-2Editorial Expression of Concern: Munc13 C2B domain is an activity-dependent Ca2+ regulator of synaptic exocytosis

Nature Structural & Molecular Biology, Published online: 03 December 2025; doi:10.1038/s41594-025-01726-yMitochondrial translational activators (TAs) facilitate transcript-specific translation. Using selective ribosome profiling and cryo-electron microscopy, the authors show that TAs bind to the 5′ untranslated region of their target transcript to position mitoribosomes for initiation.

Nature Structural & Molecular Biology, Published online: 03 December 2025; doi:10.1038/s41594-025-01724-0This Review summarizes the various functions of the exon junction complex in RNA splicing and beyond, to influence gene regulation.

Nature Structural & Molecular Biology, Published online: 03 December 2025; doi:10.1038/s41594-025-01730-2Editorial Expression of Concern: Munc13 C2B domain is an activity-dependent Ca2+ regulator of synaptic exocytosis

Nature Structural & Molecular Biology, Published online: 03 December 2025; doi:10.1038/s41594-025-01726-yMitochondrial translational activators (TAs) facilitate transcript-specific translation. Using selective ribosome profiling and cryo-electron microscopy, the authors show that TAs bind to the 5′ untranslated region of their target transcript to position mitoribosomes for initiation.

Nature Structural & Molecular Biology, Published online: 03 December 2025; doi:10.1038/s41594-025-01724-0This Review summarizes the various functions of the exon junction complex in RNA splicing and beyond, to influence gene regulation.

Nature Structural & Molecular Biology, Published online: 01 December 2025; doi:10.1038/s41594-025-01703-5Vidmar et al. use cryo-EM to reveal how bacterial RNA polymerase (RNAP) and topoisomerase I (TopoI) cooperate. TopoI switches conformation, senses DNA supercoils near RNAP and relaxes them. Mutations disrupting this process alter bacterial motility and operon polarity.

Nature Structural & Molecular Biology, Published online: 01 December 2025; doi:10.1038/s41594-025-01703-5Vidmar et al. use cryo-EM to reveal how bacterial RNA polymerase (RNAP) and topoisomerase I (TopoI) cooperate. TopoI switches conformation, senses DNA supercoils near RNAP and relaxes them. Mutations disrupting this process alter bacterial motility and operon polarity.

Nature Structural & Molecular Biology, Published online: 27 November 2025; doi:10.1038/s41594-025-01707-1By reconstituting and visualizing mammalian transcription elongation at the single-molecule level, Wang et al. dissected the effects of individual elongation factors on the speed of RNA polymerase II, which is found to operate as a multi-gear molecular machine.

Nature Structural & Molecular Biology, Published online: 27 November 2025; doi:10.1038/s41594-025-01720-4Cells store excess fat in lipid droplets to avoid lipotoxicity and maintain homeostasis. We identified an autophagy-independent role for the autophagy lipid transfer protein ATG2A in helping direct lipids to growing lipid droplets and promoting recruitment of the enzyme DGAT2. This coordination enhances triglyceride storage, protects the endoplasmic reticulum from lipid overload and limits the misrouting of lipids into other metabolic pathways.

Nature Structural & Molecular Biology, Published online: 26 November 2025; doi:10.1038/s41594-025-01716-0Rocha-Roa et al. identify TMEM170 proteins as endoplasmic reticulum lipid scramblases that partner with bridge-like lipid transfer proteins BLTP1/Csf1 proteins to enable bulk lipid transport between organelles.

Nature Structural & Molecular Biology, Published online: 27 November 2025; doi:10.1038/s41594-025-01720-4Cells store excess fat in lipid droplets to avoid lipotoxicity and maintain homeostasis. We identified an autophagy-independent role for the autophagy lipid transfer protein ATG2A in helping direct lipids to growing lipid droplets and promoting recruitment of the enzyme DGAT2. This coordination enhances triglyceride storage, protects the endoplasmic reticulum from lipid overload and limits the misrouting of lipids into other metabolic pathways.

Nature Structural & Molecular Biology, Published online: 27 November 2025; doi:10.1038/s41594-025-01707-1By reconstituting and visualizing mammalian transcription elongation at the single-molecule level, Wang et al. dissected the effects of individual elongation factors on the speed of RNA polymerase II, which is found to operate as a multi-gear molecular machine.

Nature Structural & Molecular Biology, Published online: 26 November 2025; doi:10.1038/s41594-025-01716-0Rocha-Roa et al. identify TMEM170 proteins as endoplasmic reticulum lipid scramblases that partner with bridge-like lipid transfer proteins BLTP1/Csf1 proteins to enable bulk lipid transport between organelles.

Nature Structural & Molecular Biology, Published online: 25 November 2025; doi:10.1038/s41594-025-01706-2Carty et al. identify the H3K9 methyltransferases that restrict the size and position of the centromere protein A chromatin domain, maintaining functional centromeres.

Nature Structural & Molecular Biology, Published online: 25 November 2025; doi:10.1038/s41594-025-01706-2Carty et al. identify the H3K9 methyltransferases that restrict the size and position of the centromere protein A chromatin domain, maintaining functional centromeres.

Nature Structural & Molecular Biology, Published online: 20 November 2025; doi:10.1038/s41594-025-01722-2Artificial intelligence (AI) is advancing genome editing, from predictive modeling to generative design. Emerging generative AI tools such as RFdiffusion, AlphaFold 3 and ESM now facilitate the de novo design of linkers, inhibitors and enzymes. We highlight work where AI-driven design is used to enhance the precision of mitochondrial cytosine base editors.

Nature Structural & Molecular Biology, Published online: 20 November 2025; doi:10.1038/s41594-025-01722-2Artificial intelligence (AI) is advancing genome editing, from predictive modeling to generative design. Emerging generative AI tools such as RFdiffusion, AlphaFold 3 and ESM now facilitate the de novo design of linkers, inhibitors and enzymes. We highlight work where AI-driven design is used to enhance the precision of mitochondrial cytosine base editors.

Nature Structural & Molecular Biology, Published online: 17 November 2025; doi:10.1038/s41594-025-01714-2Mi et al. use de novo protein design to address bystander and off-target editing in base editing, resulting in a highly precise mitochondrial cytosine base editor that is valuable for studying and treating mitochondrial diseases.

Nature Structural & Molecular Biology, Published online: 17 November 2025; doi:10.1038/s41594-025-01689-0Elhan et al. show that ATG2A acts with DGAT2, the enzyme producing triacylglycerol (TAG), in lipid droplet growth. By delivering diacylglycerol to lipid droplets, ATG2A not only fuels TAG production but also promotes the recruitment of DGAT2 to droplet surfaces.

Nature Structural & Molecular Biology, Published online: 17 November 2025; doi:10.1038/s41594-025-01715-1Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that FAM118A/B processing of NAD involves head-to-tail filament formation and a partnership between the two paralogs.

Nature Structural & Molecular Biology, Published online: 17 November 2025; doi:10.1038/s41594-025-01714-2Mi et al. use de novo protein design to address bystander and off-target editing in base editing, resulting in a highly precise mitochondrial cytosine base editor that is valuable for studying and treating mitochondrial diseases.

Nature Structural & Molecular Biology, Published online: 17 November 2025; doi:10.1038/s41594-025-01689-0Elhan et al. show that ATG2A acts with DGAT2, the enzyme producing triacylglycerol (TAG), in lipid droplet growth. By delivering diacylglycerol to lipid droplets, ATG2A not only fuels TAG production but also promotes the recruitment of DGAT2 to droplet surfaces.