Nature Structural & Molecular Biology, Published online: 02 January 2026; doi:10.1038/s41594-025-01729-9In this study, we applied single-particle cryogenic electron microscopy (cryo-EM) to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host-cell invasion. We assigned 40 distinct proteins to the cryo-EM densities and uncovered their spatial organization and interactions.

Nature Structural & Molecular Biology, Published online: 15 December 2025; doi:10.1038/s41594-025-01718-yHere, the authors generated and analyzed run-on sequencing data to observe transcription in species across the tree of life to uncover the origins of the promoter-proximal pause.

Nature Structural & Molecular Biology, Published online: 15 December 2025; doi:10.1038/s41594-025-01718-yHere, the authors generated and analyzed run-on sequencing data to observe transcription in species across the tree of life to uncover the origins of the promoter-proximal pause.

Nature Structural & Molecular Biology, Published online: 12 December 2025; doi:10.1038/s41594-025-01732-0We review 2025 and discuss some of the foremost initiatives developed at the journal. We also look back at discoveries we have been proud to publish.

Nature Structural & Molecular Biology, Published online: 12 December 2025; doi:10.1038/s41594-025-01732-0We review 2025 and discuss some of the foremost initiatives developed at the journal. We also look back at discoveries we have been proud to publish.

Nature Structural & Molecular Biology, Published online: 10 December 2025; doi:10.1038/s41594-025-01725-zThe AlphaFold database, released in 2022, modeled UniProt sequences from April 2021 and now provides 200 million predicted protein structures. Of the 20,504 full-length predicted human structures, 631 entries conflict with the June 2025 UniProt release. Similar conflicts across species highlight how bioinformatics resources can rapidly age.

Nature Structural & Molecular Biology, Published online: 10 December 2025; doi:10.1038/s41594-025-01725-zThe AlphaFold database, released in 2022, modeled UniProt sequences from April 2021 and now provides 200 million predicted protein structures. Of the 20,504 full-length predicted human structures, 631 entries conflict with the June 2025 UniProt release. Similar conflicts across species highlight how bioinformatics resources can rapidly age.

Nature Structural & Molecular Biology, Published online: 09 December 2025; doi:10.1038/s41594-025-01728-wZeng et al. applied single-particle cryo-electron microscopy to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host cell invasion.

Nature Structural & Molecular Biology, Published online: 08 December 2025; doi:10.1038/s41594-025-01723-1Here the authors present an artificial-intelligence-based automated method for improved protein structure determination from cryo-EM density maps by efficiently integrating map information and structure prediction.

Nature Structural & Molecular Biology, Published online: 09 December 2025; doi:10.1038/s41594-025-01728-wZeng et al. applied single-particle cryo-electron microscopy to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host cell invasion.

Nature Structural & Molecular Biology, Published online: 08 December 2025; doi:10.1038/s41594-025-01723-1Here the authors present an artificial-intelligence-based automated method for improved protein structure determination from cryo-EM density maps by efficiently integrating map information and structure prediction.

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.