Nature Structural & Molecular Biology, Published online: 30 September 2026; doi:10.1038/s41594-026-01898-1Advances in phosphoproteomics enable systems-wide mapping of phosphorylation, but translating these data into functional signaling networks remains challenging. A deep human cell-line phosphoproteome atlas infers kinase activity, enabling systematic network mapping and identification of actionable kinase vulnerabilities for precision therapies.

Nature Structural & Molecular Biology, Published online: 30 September 2026; doi:10.1038/s41594-026-01877-6Koenig et al. present a phosphoproteome atlas of 33 human cell lines covering >200,000 phosphosites, advancing cellular kinase activity scoring and drug sensitivity prediction, providing a resource for cell signaling insights and precision oncology.

Nature Structural & Molecular Biology, Published online: 29 September 2026; doi:10.1038/s41594-026-01886-5In this Review, Wu, Rashid et al. discuss how mechanical signals regulate the ability of cells to facilitate and maintain changes in cell memory. They exemplify these effects in cellular structure remodeling and epigenetic regulation.

Nature Structural & Molecular Biology, Published online: 29 September 2026; doi:10.1038/s41594-026-01886-5In this Review, Wu, Rashid et al. discuss how mechanical signals regulate the ability of cells to facilitate and maintain changes in cell memory. They exemplify these effects in cellular structure remodeling and epigenetic regulation.

Nature Structural & Molecular Biology, Published online: 28 September 2026; doi:10.1038/s41594-026-01889-2The authors use selective ribosome profiling, cryo-ET and site-specific photocrosslinking to show how the ER membrane protein complex (EMC) cooperates with ribosome-bound translocons to facilitate multipass membrane protein biogenesis in human cells.

Nature Structural & Molecular Biology, Published online: 28 September 2026; doi:10.1038/s41594-026-01897-2The authors expand the extracellular vesicle glycosylated RNA (glycoRNA) landscape and reveal distinct glycoRNA profiles across extracellular vesicle (EV) subtypes, cell types and passage numbers. They also show that glycoRNAs are not only EV cargoes but also regulators of EV uptake, uncovering a layer of vesicle-mediated communication.

Nature Structural & Molecular Biology, Published online: 28 September 2026; doi:10.1038/s41594-026-01871-yLu and Du et al. show that HERC4 E3 ligase ubiquitinates S166-phosphorylated RIPK1 to initiate prodeath complex assembly and TNF-induced cell death, acting as the pivotal prodeath switch and that loss of HERC4 protects mice from TNF-driven inflammation and liver injury.

Nature Structural & Molecular Biology, Published online: 28 September 2026; doi:10.1038/s41594-026-01889-2The authors use selective ribosome profiling, cryo-ET and site-specific photocrosslinking to show how the ER membrane protein complex (EMC) cooperates with ribosome-bound translocons to facilitate multipass membrane protein biogenesis in human cells.

Nature Structural & Molecular Biology, Published online: 28 September 2026; doi:10.1038/s41594-026-01897-2The authors expand the extracellular vesicle glycosylated RNA (glycoRNA) landscape and reveal distinct glycoRNA profiles across extracellular vesicle (EV) subtypes, cell types and passage numbers. They also show that glycoRNAs are not only EV cargoes but also regulators of EV uptake, uncovering a layer of vesicle-mediated communication.

Nature Structural & Molecular Biology, Published online: 28 September 2026; doi:10.1038/s41594-026-01871-yLu and Du et al. show that HERC4 E3 ligase ubiquitinates S166-phosphorylated RIPK1 to initiate prodeath complex assembly and TNF-induced cell death, acting as the pivotal prodeath switch and that loss of HERC4 protects mice from TNF-driven inflammation and liver injury.

Nature Structural & Molecular Biology, Published online: 22 September 2026; doi:10.1038/s41594-026-01880-xThe lumen geometry and chemistry of a protein nanopore govern its ion-conduction properties. Rather than redesigning an entire pore assembly, or mutating a naturally occurring pore, we built on the bacterial CsgG nanopore scaffold with an integral de novo component, which yielded semisynthetic conducting pores with programmed architecture and distinct ion-conduction profiles, including rectifying behavior.

Nature Structural & Molecular Biology, Published online: 22 September 2026; doi:10.1038/s41594-026-01880-xThe lumen geometry and chemistry of a protein nanopore govern its ion-conduction properties. Rather than redesigning an entire pore assembly, or mutating a naturally occurring pore, we built on the bacterial CsgG nanopore scaffold with an integral de novo component, which yielded semisynthetic conducting pores with programmed architecture and distinct ion-conduction profiles, including rectifying behavior.

Nature Structural & Molecular Biology, Published online: 21 September 2026; doi:10.1038/s41594-026-01881-wSchnaider et al. develop a protein design strategy for building a new component within a confined, symmetric pore. Cryo-EM confirms the designed lumen architecture, while electrical recordings reveal distinct and tunable current rectification.

Nature Structural & Molecular Biology, Published online: 21 September 2026; doi:10.1038/s41594-026-01881-wSchnaider et al. develop a protein design strategy for building a new component within a confined, symmetric pore. Cryo-EM confirms the designed lumen architecture, while electrical recordings reveal distinct and tunable current rectification.

Nature Structural & Molecular Biology, Published online: 17 September 2026; doi:10.1038/s41594-026-01899-0The ATR–ATRIP kinase complex safeguards genome integrity by coordinating cellular responses to DNA damage and replication stress. Two recent cryo-EM studies resolve the structural basis of ATR–ATRIP activation, capturing distinct active states of the kinase and clarifying how its activity is stimulated by TOPBP1 and ETAA1.

Nature Structural & Molecular Biology, Published online: 17 September 2026; doi:10.1038/s41594-026-01887-4Wang et al. present cryo-electron microscopy structures of ATR–ATRIP complexes in distinct functional states, revealing ATP-dependent and TopBP1-dependent mechanisms of kinase activation and how ATR inhibitors exploit ATP-binding pocket flexibility for selective inhibition.

Nature Structural & Molecular Biology, Published online: 16 September 2026; doi:10.1038/s41594-026-01890-9The authors identified and engineered a miniature, innate nuclease-dead xCas12m enabling effective epigenome editing. xCas12m–CRISPRoff achieved durable epigenetic silencing and inhibition of hepatitis B virus infection through single-AAV delivery.

Nature Structural & Molecular Biology, Published online: 17 September 2026; doi:10.1038/s41594-026-01899-0The ATR–ATRIP kinase complex safeguards genome integrity by coordinating cellular responses to DNA damage and replication stress. Two recent cryo-EM studies resolve the structural basis of ATR–ATRIP activation, capturing distinct active states of the kinase and clarifying how its activity is stimulated by TOPBP1 and ETAA1.

Nature Structural & Molecular Biology, Published online: 17 September 2026; doi:10.1038/s41594-026-01887-4Wang et al. present cryo-electron microscopy structures of ATR–ATRIP complexes in distinct functional states, revealing ATP-dependent and TopBP1-dependent mechanisms of kinase activation and how ATR inhibitors exploit ATP-binding pocket flexibility for selective inhibition.

Nature Structural & Molecular Biology, Published online: 16 September 2026; doi:10.1038/s41594-026-01890-9The authors identified and engineered a miniature, innate nuclease-dead xCas12m enabling effective epigenome editing. xCas12m–CRISPRoff achieved durable epigenetic silencing and inhibition of hepatitis B virus infection through single-AAV delivery.

Nature Structural & Molecular Biology, Published online: 14 September 2026; doi:10.1038/s41594-026-01885-6Ciapponi et al. determine the cryo-electron microscopy structure of the canonical Polycomb repressive complex 1 holocomplex and show how its architecture coordinates complex assembly, H2A monoubiquitination and genomic targeting.

Nature Structural & Molecular Biology, Published online: 14 September 2026; doi:10.1038/s41594-026-01885-6Ciapponi et al. determine the cryo-electron microscopy structure of the canonical Polycomb repressive complex 1 holocomplex and show how its architecture coordinates complex assembly, H2A monoubiquitination and genomic targeting.

Nature Structural & Molecular Biology, Published online: 11 September 2026; doi:10.1038/s41594-026-01888-3Structured RNA virus genomes

Nature Structural & Molecular Biology, Published online: 11 September 2026; doi:10.1038/s41594-026-01892-7Mammalian life begins with oocytes and sperm cells, but our understanding of the molecular mechanisms endowing these cells with their unique properties has lagged behind. In this Editorial, our team emphasizes the need and our wish to improve our knowledge in how these cells operate.

Nature Structural & Molecular Biology, Published online: 10 September 2026; doi:10.1038/s41594-026-01884-7Wang et al. show that the UT3 domain of Ufd1 binds to and unfolds K48-linked polyubiquitin chains without ATP. Simultaneous binding of two ubiquitins to UT3 is key to overcome the energy barrier. This ubiquitin unfolding is critical for Cdc48/p97’s function.

Nature Structural & Molecular Biology, Published online: 09 September 2026; doi:10.1038/s41594-026-01894-5Ocampo and Orosco et al. present the cryo-electron microscopy structure of Acidaminococcus sp. Cas12a bound to a pseudo-DNA guide and RNA target, showing how structural mimicry enables DNA-guided RNA recognition, providing a blueprint for engineering CRISPR–Cas systems.

Nature Structural & Molecular Biology, Published online: 09 September 2026; doi:10.1038/s41594-026-01882-9AMPA receptor (AMPAR) gating proceeds through an intermediate pre-active state that has structurally remained an enigma. Here, Newton et al. use full and partial agonists and time-resolved cryo-electron microscopy to resolve this state and reveal the complete gating pathway of AMPARs.

Nature Structural & Molecular Biology, Published online: 10 September 2026; doi:10.1038/s41594-026-01884-7Wang et al. show that the UT3 domain of Ufd1 binds to and unfolds K48-linked polyubiquitin chains without ATP. Simultaneous binding of two ubiquitins to UT3 is key to overcome the energy barrier. This ubiquitin unfolding is critical for Cdc48/p97’s function.

Nature Structural & Molecular Biology, Published online: 08 September 2026; doi:10.1038/s41594-026-01878-5Cui, Sheng and colleagues present cryo-EM structures of human NLRP6 monomer in the ATP/NBD-bound and ATP/NBD-unbound conformations, revealing the detailed mechanisms of how ATP acts as an endogenous inhibitor of the NLRP6 inflammasome.

Nature Structural & Molecular Biology, Published online: 09 September 2026; doi:10.1038/s41594-026-01894-5Ocampo and Orosco et al. present the cryo-electron microscopy structure of Acidaminococcus sp. Cas12a bound to a pseudo-DNA guide and RNA target, showing how structural mimicry enables DNA-guided RNA recognition, providing a blueprint for engineering CRISPR–Cas systems.

Nature Structural & Molecular Biology, Published online: 09 September 2026; doi:10.1038/s41594-026-01882-9AMPA receptor (AMPAR) gating proceeds through an intermediate pre-active state that has structurally remained an enigma. Here, Newton et al. use full and partial agonists and time-resolved cryo-electron microscopy to resolve this state and reveal the complete gating pathway of AMPARs.

Nature Structural & Molecular Biology, Published online: 08 September 2026; doi:10.1038/s41594-026-01878-5Cui, Sheng and colleagues present cryo-EM structures of human NLRP6 monomer in the ATP/NBD-bound and ATP/NBD-unbound conformations, revealing the detailed mechanisms of how ATP acts as an endogenous inhibitor of the NLRP6 inflammasome.

Nature Structural & Molecular Biology, Published online: 01 September 2026; doi:10.1038/s41594-026-01870-zProteasomes are essential for male fertility. Kolata, dos Santos, Dendooven and colleagues show large nuclear proteasomal assemblies segregated from DNA in human sperm, forming after meiosis and with a unique α4s isoform. A native substrate is bound at the 20S catalytic site.

Nature Structural & Molecular Biology, Published online: 31 August 2026; doi:10.1038/s41594-026-01872-xNewly imported mitochondrial proteins are trimmed to their mature form by processing peptidases; for a subset, ICP55 removes a single further amino acid from the N terminus. Kücükköse et al. now identify the substrates of human ICP55, using the HUNTER method, and show that this single cleavage is required for the stability of mitochondrial protein complexes.

Nature Structural & Molecular Biology, Published online: 31 August 2026; doi:10.1038/s41594-026-01876-7Kücükköse, Luzarowski and colleagues show that removing a single N-terminal amino acid during the maturation of newly imported mitochondrial proteins globally stabilizes mitochondrial protein complexes, revealing an unexpected layer of regulation of mitochondrial proteostasis.

Nature Structural & Molecular Biology, Published online: 31 August 2026; doi:10.1038/s41594-026-01879-4Watanabe et al. show that tau fibrils from Alzheimer disease and vacuolar tauopathy exhibit distinct seeding patterns in vivo. Cryo-electron microscopy reveals that modifications outside the ordered core can remodel tau fibril ultrastructure, with polyubiquitin repositioning of vacuolar tauopathy fibrils shifting the protofilament interface.

Nature Structural & Molecular Biology, Published online: 01 September 2026; doi:10.1038/s41594-026-01870-zProteasomes are essential for male fertility. Kolata, dos Santos, Dendooven and colleagues show large nuclear proteasomal assemblies segregated from DNA in human sperm, forming after meiosis and with a unique α4s isoform. A native substrate is bound at the 20S catalytic site.

Nature Structural & Molecular Biology, Published online: 31 August 2026; doi:10.1038/s41594-026-01872-xNewly imported mitochondrial proteins are trimmed to their mature form by processing peptidases; for a subset, ICP55 removes a single further amino acid from the N terminus. Kücükköse et al. now identify the substrates of human ICP55, using the HUNTER method, and show that this single cleavage is required for the stability of mitochondrial protein complexes.

Nature Structural & Molecular Biology, Published online: 31 August 2026; doi:10.1038/s41594-026-01876-7Kücükköse, Luzarowski and colleagues show that removing a single N-terminal amino acid during the maturation of newly imported mitochondrial proteins globally stabilizes mitochondrial protein complexes, revealing an unexpected layer of regulation of mitochondrial proteostasis.

Nature Structural & Molecular Biology, Published online: 31 August 2026; doi:10.1038/s41594-026-01879-4Watanabe et al. show that tau fibrils from Alzheimer disease and vacuolar tauopathy exhibit distinct seeding patterns in vivo. Cryo-electron microscopy reveals that modifications outside the ordered core can remodel tau fibril ultrastructure, with polyubiquitin repositioning of vacuolar tauopathy fibrils shifting the protofilament interface.

Nature Structural & Molecular Biology, Published online: 28 August 2026; doi:10.1038/s41594-026-01866-9Kim et al. present cryo-EM structures of GluN1–GluN3A NMDA receptors with complementary electrophysiology, revealing structure-based mechanisms of receptor gating, paradoxical potentiation by a GluN1-selective antagonist and allosteric modulation.

Nature Structural & Molecular Biology, Published online: 28 August 2026; doi:10.1038/s41594-026-01869-6Kojima et al. introduce NOAH–ARK1, a universal pipeline combining computational screening and a de novo designed fusion protein to reduce construct optimization effort and enable rapid high-resolution G-protein-coupled receptor structure determination for drug discovery.

Nature Structural & Molecular Biology, Published online: 28 August 2026; doi:10.1038/s41594-026-01866-9Kim et al. present cryo-EM structures of GluN1–GluN3A NMDA receptors with complementary electrophysiology, revealing structure-based mechanisms of receptor gating, paradoxical potentiation by a GluN1-selective antagonist and allosteric modulation.

Nature Structural & Molecular Biology, Published online: 28 August 2026; doi:10.1038/s41594-026-01869-6Kojima et al. introduce NOAH–ARK1, a universal pipeline combining computational screening and a de novo designed fusion protein to reduce construct optimization effort and enable rapid high-resolution G-protein-coupled receptor structure determination for drug discovery.

Nature Structural & Molecular Biology, Published online: 26 August 2026; doi:10.1038/s41594-026-01868-7Phenylalanine–glycine repeats in nuclear pore complexes establish the nucleocytoplasmic permeability barrier. These intrinsically disordered protein segments may act as ‘molecular wedges’ that expand during postmitotic assembly, linking re-establishment of nucleocytoplasmic transport with nuclear envelope re-formation at the end of mitosis.

Nature Structural & Molecular Biology, Published online: 26 August 2026; doi:10.1038/s41594-026-01873-wSlivka et al. track dynein’s microtubule-binding domain with minimal fluorescence photon flux, revealing transient backward ‘dips’ before steps. These dips represent microtubule release upon ATP binding and diffusional search, terminating in net forward bias driven by ATP hydrolysis.

Nature Structural & Molecular Biology, Published online: 26 August 2026; doi:10.1038/s41594-026-01868-7Phenylalanine–glycine repeats in nuclear pore complexes establish the nucleocytoplasmic permeability barrier. These intrinsically disordered protein segments may act as ‘molecular wedges’ that expand during postmitotic assembly, linking re-establishment of nucleocytoplasmic transport with nuclear envelope re-formation at the end of mitosis.

Nature Structural & Molecular Biology, Published online: 26 August 2026; doi:10.1038/s41594-026-01873-wSlivka et al. track dynein’s microtubule-binding domain with minimal fluorescence photon flux, revealing transient backward ‘dips’ before steps. These dips represent microtubule release upon ATP binding and diffusional search, terminating in net forward bias driven by ATP hydrolysis.

Nature Structural & Molecular Biology, Published online: 24 August 2026; doi:10.1038/s41594-026-01874-9The therapeutic and reinforcing mechanisms of ketamine have been historically attributed to NMDAR (N-methyl-d-aspartate receptor) antagonism. A study now shows that ketamine binds noncanonically to opioid receptors at their orthosteric sites, acts as a partial opioid receptor agonist, and produces opioid receptor-dependent analgesia.

Nature Structural & Molecular Biology, Published online: 24 August 2026; doi:10.1038/s41594-026-01874-9The therapeutic and reinforcing mechanisms of ketamine have been historically attributed to NMDAR (N-methyl-d-aspartate receptor) antagonism. A study now shows that ketamine binds noncanonically to opioid receptors at their orthosteric sites, acts as a partial opioid receptor agonist, and produces opioid receptor-dependent analgesia.