New online: Predicting RNA cellular activity

Many ligands and states of bitter taste GPCRs Nature Structural & Molecular Biology, Published online: 20 April 2026; doi:10.1038/s41594-026-01790-yBitter taste receptors are a subtype of G-protein receptors that are activated by a variety of ligands, leading to bitter taste sensation. Two studies now report new details of ligand binding by the human TAS2R43, TAS2R14 and TAS2R46 receptors.

New online: Many ligands and states of bitter taste GPCRs

Cracking the code of native amyloid fibrils: advances and next steps to enable pathology-informed therapeutic and diagnostic Nature Structural & Molecular Biology, Published online: 20 April 2026; doi:10.1038/s41594-026-01792-wHere, the author describes advances in understanding structures and post-translational modifications of amyloid fibrils through various techniques and the degree to which they recapitulate physiology and pathology, to better guide method selection when designing therapeutic or diagnostic interventions.

New online: Cracking the code of native amyloid fibrils: advances and next steps to enable pathology-informed therapeutic and diagnostic

Structural insights into coffee bitter taste perception by TAS2R43 receptor Nature Structural & Molecular Biology, Published online: 20 April 2026; doi:10.1038/s41594-026-01776-wKim et al. revealed how taste receptor type 2 member 43, a bitter taste receptor that detects coffee-derived compounds, recognizes bitter tastants through cryo-electron microscopy structures of ligand-bound complexes, supported by biochemical and computational analyses, providing a structural framework for coffee bitter taste signaling.

New online: Structural insights into coffee bitter taste perception by TAS2R43 receptor

Ligand binding modes of the bitter taste receptor T2R14 and T2R46 Nature Structural & Molecular Biology, Published online: 20 April 2026; doi:10.1038/s41594-026-01786-8Tan, Yu, Han et al. show how human bitter taste receptors recognize diverse ligands by determining several T2R structures. The study presents distinct binding modes and an intrinsic activation mechanism.

New online: Ligand binding modes of the bitter taste receptor T2R14 and T2R46

Calcium dependent activation of the TMEM16F scramblase and ion channel Nature Structural & Molecular Biology, Published online: 17 April 2026; doi:10.1038/s41594-026-01789-5Feng, Alvarenga et al. use cryo-electron microscopy to visualize the activation of the transmembrane protein 16F channel and scramblase in liposomes to show that it adopts a conformation that forms separate pathways for ions and lipids, thereby rationalizing its dual activity.

ICYMI: New online: Calcium dependent activation of the TMEM16F scramblase and ion channel

Calcium dependent activation of the TMEM16F scramblase and ion channel Nature Structural & Molecular Biology, Published online: 17 April 2026; doi:10.1038/s41594-026-01789-5Feng, Alvarenga et al. use cryo-electron microscopy to visualize the activation of the transmembrane protein 16F channel and scramblase in liposomes to show that it adopts a conformation that forms separate pathways for ions and lipids, thereby rationalizing its dual activity.

New online: Calcium dependent activation of the TMEM16F scramblase and ion channel

Comparative characterization of Cas12f orthologs reveals mechanistic features underlying enhanced genome editing efficiency Nature Structural & Molecular Biology, Published online: 13 April 2026; doi:10.1038/s41594-026-01788-6Guan, Ocampo and colleagues report the discovery and mechanistic dissection of Al3Cas12f, a metagenome-derived miniature nuclease that retains notable genome-editing capacity. They engineer an RKK variant, which boosts editing and helps overcome the potency threshold that has limited compact editors.

ICYMI: New online: Comparative characterization of Cas12f orthologs reveals mechanistic features underlying enhanced genome editing efficiency

Comparative characterization of Cas12f orthologs reveals mechanistic features underlying enhanced genome editing efficiency Nature Structural & Molecular Biology, Published online: 13 April 2026; doi:10.1038/s41594-026-01788-6Guan, Ocampo and colleagues report the discovery and mechanistic dissection of Al3Cas12f, a metagenome-derived miniature nuclease that retains notable genome-editing capacity. They engineer an RKK variant, which boosts editing and helps overcome the potency threshold that has limited compact editors.

New online: Comparative characterization of Cas12f orthologs reveals mechanistic features underlying enhanced genome editing efficiency

MitoPerturb-Seq identifies links between nuclear and mitochondrial genomes in single cells Nature Structural & Molecular Biology, Published online: 09 April 2026; doi:10.1038/s41594-026-01780-0The replication, transcription and quality control of mitochondrial DNA are tightly regulated by nuclear-encoded mitochondrial proteins. We developed MitoPerturb-Seq, a high-throughput single-cell approach to interrogate these nuclear–mitochondrial interactions. This method revealed cellular responses to the depletion of mitochondrial DNA, indicating that it will enable the discovery of cell-type specific vulnerabilities to mitochondrial dysfunction.

ICYMI: New online: MitoPerturb-Seq identifies links between nuclear and mitochondrial genomes in single cells

MitoPerturb-Seq identifies links between nuclear and mitochondrial genomes in single cells Nature Structural & Molecular Biology, Published online: 09 April 2026; doi:10.1038/s41594-026-01780-0The replication, transcription and quality control of mitochondrial DNA are tightly regulated by nuclear-encoded mitochondrial proteins. We developed MitoPerturb-Seq, a high-throughput single-cell approach to interrogate these nuclear–mitochondrial interactions. This method revealed cellular responses to the depletion of mitochondrial DNA, indicating that it will enable the discovery of cell-type specific vulnerabilities to mitochondrial dysfunction.

New online: MitoPerturb-Seq identifies links between nuclear and mitochondrial genomes in single cells

A two-step mechanism for sugar translocation Nature Structural & Molecular Biology, Published online: 08 April 2026; doi:10.1038/s41594-026-01784-wSugar porters are textbook examples of how transport activity is described by Michaelis–Menten kinetics. Here, using saturation transfer difference nuclear magnetic resonance spectroscopy, Ahn et al. conclude that the fully occluded state of a sugar transporter is analogous to the transition state in soluble enzymes.

ICYMI: New online: A two-step mechanism for sugar translocation

Microtubules in the axon are GDP bound but adopt a stable GTP-like expanded state Nature Structural & Molecular Biology, Published online: 08 April 2026; doi:10.1038/s41594-026-01787-7Zehr et al. revealed the 2.7-Å cryo-electron microscopy reconstruction of human microtubules in situ in the axon of induced pluripotent stem cell (iPS cell)-derived neurons. It shows an expanded microtubule lattice yet bound to GDP, in contrast to the compacted lattice observed at the iPS cell stage.

ICYMI: New online: Microtubules in the axon are GDP bound but adopt a stable GTP-like expanded state

A two-step mechanism for sugar translocation Nature Structural & Molecular Biology, Published online: 08 April 2026; doi:10.1038/s41594-026-01784-wSugar porters are textbook examples of how transport activity is described by Michaelis–Menten kinetics. Here, using saturation transfer difference nuclear magnetic resonance spectroscopy, Ahn et al. conclude that the fully occluded state of a sugar transporter is analogous to the transition state in soluble enzymes.

New online: A two-step mechanism for sugar translocation

Microtubules in the axon are GDP bound but adopt a stable GTP-like expanded state Nature Structural & Molecular Biology, Published online: 08 April 2026; doi:10.1038/s41594-026-01787-7Zehr et al. revealed the 2.7-Å cryo-electron microscopy reconstruction of human microtubules in situ in the axon of induced pluripotent stem cell (iPS cell)-derived neurons. It shows an expanded microtubule lattice yet bound to GDP, in contrast to the compacted lattice observed at the iPS cell stage.

New online: Microtubules in the axon are GDP bound but adopt a stable GTP-like expanded state

ICYMI: New online: Challenges of studying signaling metabolites in early development

New online: Challenges of studying signaling metabolites in early development

RNA damage signaling primes transcription-coupled repair Nature Structural & Molecular Biology, Published online: 01 April 2026; doi:10.1038/s41594-026-01782-yTo ensure accurate gene expression, transcription-coupled repair (TCR) clears DNA transcription blocks, yet genotoxic insults also damage RNA. A study shows that Integrator subunit INTS12 is a key mediator linking ribosome-mediated damage signaling to TCR, with stress-induced phosphorylation promoting clearance of stalled RNA polymerase II.

ICYMI: New online: RNA damage signaling primes transcription-coupled repair

MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy Nature Structural & Molecular Biology, Published online: 01 April 2026; doi:10.1038/s41594-026-01779-7Burr and Auckland et. al develop MitoPerturb-Seq, which combines single-cell screening with multiomics to link nuclear genes to mitochondrial DNA (mtDNA) dynamics. They unveil core regulators of mtDNA copy number and characterize cell-cycle delays and transcriptional stress in response to mtDNA depletion.

ICYMI: New online: MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy

Resolution of R-loops and transcription–replication conflicts by SETX–BRCA1–BARD1 complex Nature Structural & Molecular Biology, Published online: 31 March 2026; doi:10.1038/s41594-026-01778-8Dutta et al. demonstrate that the tumor suppressor complex BRCA1–BARD1 physically interacts with the RNA–DNA helicase Senataxin (SETX) and upregulates the activity of SETX to resolve harmful R-loops crucial for the avoidance of transcription–replication conflicts.

ICYMI: New online: Resolution of R-loops and transcription–replication conflicts by SETX–BRCA1–BARD1 complex

Condensate protein aggregation in ALS/FTD is regulated by GGGGCC-repeat RNA scaffolds Nature Structural & Molecular Biology, Published online: 31 March 2026; doi:10.1038/s41594-026-01785-9Liu et al. show that the C9orf72 GGGGCC-repeat RNA drives liquid-to-solid phase transition of poly(GR) in ALS/FTD through forming G-quadruplex and hairpin scaffolds, whereas targeting the RNA structures with small molecules reduces poly(GR) aggregation and cellular dysfunction.

ICYMI: New online: Condensate protein aggregation in ALS/FTD is regulated by GGGGCC-repeat RNA scaffolds

RNA damage signaling primes transcription-coupled repair Nature Structural & Molecular Biology, Published online: 01 April 2026; doi:10.1038/s41594-026-01782-yTo ensure accurate gene expression, transcription-coupled repair (TCR) clears DNA transcription blocks, yet genotoxic insults also damage RNA. A study shows that Integrator subunit INTS12 is a key mediator linking ribosome-mediated damage signaling to TCR, with stress-induced phosphorylation promoting clearance of stalled RNA polymerase II.

New online: RNA damage signaling primes transcription-coupled repair

MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy Nature Structural & Molecular Biology, Published online: 01 April 2026; doi:10.1038/s41594-026-01779-7Burr and Auckland et. al develop MitoPerturb-Seq, which combines single-cell screening with multiomics to link nuclear genes to mitochondrial DNA (mtDNA) dynamics. They unveil core regulators of mtDNA copy number and characterize cell-cycle delays and transcriptional stress in response to mtDNA depletion.

New online: MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy

Resolution of R-loops and transcription–replication conflicts by SETX–BRCA1–BARD1 complex Nature Structural & Molecular Biology, Published online: 31 March 2026; doi:10.1038/s41594-026-01778-8Dutta et al. demonstrate that the tumor suppressor complex BRCA1–BARD1 physically interacts with the RNA–DNA helicase Senataxin (SETX) and upregulates the activity of SETX to resolve harmful R-loops crucial for the avoidance of transcription–replication conflicts.

New online: Resolution of R-loops and transcription–replication conflicts by SETX–BRCA1–BARD1 complex

Condensate protein aggregation in ALS/FTD is regulated by GGGGCC-repeat RNA scaffolds Nature Structural & Molecular Biology, Published online: 31 March 2026; doi:10.1038/s41594-026-01785-9Liu et al. show that the C9orf72 GGGGCC-repeat RNA drives liquid-to-solid phase transition of poly(GR) in ALS/FTD through forming G-quadruplex and hairpin scaffolds, whereas targeting the RNA structures with small molecules reduces poly(GR) aggregation and cellular dysfunction.

New online: Condensate protein aggregation in ALS/FTD is regulated by GGGGCC-repeat RNA scaffolds

Structural insight into IscB’s RNA-lid-based inactivation mechanism Nature Structural & Molecular Biology, Published online: 25 March 2026; doi:10.1038/s41594-026-01761-3Wang, Guo, Zhang and colleagues obtain four cryo-electron microscopy snapshots that show how IscB is kept off by two RNA lids, with a car-pedal-like guide shift activating cleavage after ~11-nt pairing. They also engineer hinge regions that boost flexibility and improve genome editing in cells.

ICYMI: New online: Structural insight into IscB’s RNA-lid-based inactivation mechanism

Structural insight into IscB’s RNA-lid-based inactivation mechanism Nature Structural & Molecular Biology, Published online: 25 March 2026; doi:10.1038/s41594-026-01761-3Wang, Guo, Zhang and colleagues obtain four cryo-electron microscopy snapshots that show how IscB is kept off by two RNA lids, with a car-pedal-like guide shift activating cleavage after ~11-nt pairing. They also engineer hinge regions that boost flexibility and improve genome editing in cells.

New online: Structural insight into IscB’s RNA-lid-based inactivation mechanism

Extending guide RNA length restores high-fidelity CRISPR–Cas9 activity Nature Structural & Molecular Biology, Published online: 20 March 2026; doi:10.1038/s41594-026-01765-zHigh-fidelity CRISPR–Cas9 enzymes have fewer off-targets but often suffer from low editing efficiency. Here, we show that a simple extension of the guide RNA improves the activity of SuperFi-Cas9 while preserving its accuracy. This extension enhances SuperFi-Cas9’s genome editing performance by strengthening the interactions in the protospacer adjacent motif (PAM)-distal region.

ICYMI: New online: Extending guide RNA length restores high-fidelity CRISPR–Cas9 activity

Extending guide RNA length restores high-fidelity CRISPR–Cas9 activity Nature Structural & Molecular Biology, Published online: 20 March 2026; doi:10.1038/s41594-026-01765-zHigh-fidelity CRISPR–Cas9 enzymes have fewer off-targets but often suffer from low editing efficiency. Here, we show that a simple extension of the guide RNA improves the activity of SuperFi-Cas9 while preserving its accuracy. This extension enhances SuperFi-Cas9’s genome editing performance by strengthening the interactions in the protospacer adjacent motif (PAM)-distal region.

New online: Extending guide RNA length restores high-fidelity CRISPR–Cas9 activity

No stasis in proteostasis Nature Structural & Molecular Biology, Published online: 18 March 2026; doi:10.1038/s41594-026-01783-xIn this issue of Nature Structural & Molecular Biology, we focus on all things protein homeostasis, highlighting a variety of processes, from protein quality control in translation to autophagy.

ICYMI: New online: No stasis in proteostasis