Nature Structural & Molecular Biology, Published online: 14 October 2025; doi:10.1038/s41594-025-01677-4Li et al. show that a Lamassu defense system protects bacteria from phage infection by activating a lethal tetrameric DNA-cutting enzyme. In the absence of phages, a protein clamp holds the enzyme as an inactive monomer, preventing self-damage.

Nature Structural & Molecular Biology, Published online: 10 October 2025; doi:10.1038/s41594-025-01649-8Using a new method called FoldTree, the authors compare proteins on the basis of their shape to construct more accurate family trees over long evolutionary timescales and capture distant relationships where sequence information becomes less reliable.

Nature Structural & Molecular Biology, Published online: 10 October 2025; doi:10.1038/s41594-025-01649-8Using a new method called FoldTree, the authors compare proteins on the basis of their shape to construct more accurate family trees over long evolutionary timescales and capture distant relationships where sequence information becomes less reliable.

Nature Structural & Molecular Biology, Published online: 09 October 2025; doi:10.1038/s41594-025-01684-5Fu et al. uncover the features that allow the HIV capsid to cross the permeability barrier of nuclear pores in an importin-independent manner, explaining how the viral genome can reach the nuclear compartment when infecting nondividing cells.

Nature Structural & Molecular Biology, Published online: 09 October 2025; doi:10.1038/s41594-025-01684-5Fu et al. uncover the features that allow the HIV capsid to cross the permeability barrier of nuclear pores in an importin-independent manner, explaining how the viral genome can reach the nuclear compartment when infecting nondividing cells.

Nature Structural & Molecular Biology, Published online: 06 October 2025; doi:10.1038/s41594-025-01645-yExile, discovery, and resilience have shaped my journey as a group leader in Mexico. From exploring chromatin architecture to building a lab and community, this is how science became my vocation and my home.

Nature Structural & Molecular Biology, Published online: 06 October 2025; doi:10.1038/s41594-025-01686-3Here Schwämmle et al. develop CRISPR reporter screens to map transcription-factor-regulatory element interactions at the Xist locus, revealing a two-step mechanism integrating developmental and X-dosage signals to initiate X-chromosome inactivation.

Nature Structural & Molecular Biology, Published online: 06 October 2025; doi:10.1038/s41594-025-01645-yExile, discovery, and resilience have shaped my journey as a group leader in Mexico. From exploring chromatin architecture to building a lab and community, this is how science became my vocation and my home.

Nature Structural & Molecular Biology, Published online: 06 October 2025; doi:10.1038/s41594-025-01686-3Here Schwämmle et al. develop CRISPR reporter screens to map transcription-factor-regulatory element interactions at the Xist locus, revealing a two-step mechanism integrating developmental and X-dosage signals to initiate X-chromosome inactivation.

Nature Structural & Molecular Biology, Published online: 29 September 2025; doi:10.1038/s41594-025-01680-9Issa et al. show that the ciliary small guanosine triphosphatase Arl3 displaces the inhibitory regulator Shulin/DNAAF9 from the outer dynein arm, leading to motor activation.

Nature Structural & Molecular Biology, Published online: 29 September 2025; doi:10.1038/s41594-025-01680-9Issa et al. show that the ciliary small guanosine triphosphatase Arl3 displaces the inhibitory regulator Shulin/DNAAF9 from the outer dynein arm, leading to motor activation.

Nature Structural & Molecular Biology, Published online: 26 September 2025; doi:10.1038/s41594-025-01682-7Inhibitors of ferroptosis are key tools for studies of cell death and may ultimately prove useful for the treatment of various diseases. In this Comment, we discuss major types of ferroptosis inhibitors and considerations for their use in mechanistic and preclinical studies.

Nature Structural & Molecular Biology, Published online: 25 September 2025; doi:10.1038/s41594-025-01681-8This study reveals how human small ubiquitin-like modifier (SUMO) E1 recruits its E2 partner UBC9 and transfers SUMO1 through large structural changes, uncovering key mechanisms that ensure specificity and fidelity in SUMOylation, an essential protein modification pathway.

Nature Structural & Molecular Biology, Published online: 26 September 2025; doi:10.1038/s41594-025-01682-7Inhibitors of ferroptosis are key tools for studies of cell death and may ultimately prove useful for the treatment of various diseases. In this Comment, we discuss major types of ferroptosis inhibitors and considerations for their use in mechanistic and preclinical studies.

Nature Structural & Molecular Biology, Published online: 25 September 2025; doi:10.1038/s41594-025-01681-8This study reveals how human small ubiquitin-like modifier (SUMO) E1 recruits its E2 partner UBC9 and transfers SUMO1 through large structural changes, uncovering key mechanisms that ensure specificity and fidelity in SUMOylation, an essential protein modification pathway.

Nature Structural & Molecular Biology, Published online: 22 September 2025; doi:10.1038/s41594-025-01659-6Many mutations cause disease because they destabilize proteins. Here, Mighell and Lehner show that a single small molecule can correct the destabilization caused by nearly all pathogenic mutations in a human GPCR.

Nature Structural & Molecular Biology, Published online: 22 September 2025; doi:10.1038/s41594-025-01659-6Many mutations cause disease because they destabilize proteins. Here, Mighell and Lehner show that a single small molecule can correct the destabilization caused by nearly all pathogenic mutations in a human GPCR.

Nature Structural & Molecular Biology, Published online: 19 September 2025; doi:10.1038/s41594-025-01676-5By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

Nature Structural & Molecular Biology, Published online: 18 September 2025; doi:10.1038/s41594-025-01646-xCell death contributes to tissue homeostasis and plays critical roles in inflammation and host defense. Our increasing understanding of the physiological importance of cell death underlines the need to more fully elucidate its underlying mechanisms in health and disease. Molecular and structural insight into the cell death apparatus could provide strategies to target the loss of cells in pathophysiological contexts. We asked experts studying a range of cell death types to share with us what they are most excited to tackle and what the field needs for progress.

Nature Structural & Molecular Biology, Published online: 19 September 2025; doi:10.1038/s41594-025-01676-5By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

Nature Structural & Molecular Biology, Published online: 18 September 2025; doi:10.1038/s41594-025-01646-xCell death contributes to tissue homeostasis and plays critical roles in inflammation and host defense. Our increasing understanding of the physiological importance of cell death underlines the need to more fully elucidate its underlying mechanisms in health and disease. Molecular and structural insight into the cell death apparatus could provide strategies to target the loss of cells in pathophysiological contexts. We asked experts studying a range of cell death types to share with us what they are most excited to tackle and what the field needs for progress.

Nature Structural & Molecular Biology, Published online: 16 September 2025; doi:10.1038/s41594-025-01672-9We highlight primary research and commissioned content that delve into the biology of ubiquitylation and degradation mechanisms.

Nature Structural & Molecular Biology, Published online: 16 September 2025; doi:10.1038/s41594-025-01678-3Fujioka et al. show that, under starvation, yeast Atg1 forms droplets that concentrate autophagy factors, boosting Atg8 lipidation and clustering vesicles. These droplets likely serve as hubs that generate membrane seeds for autophagosome formation.

We highlight primary research and commissioned content that delve into the biology of ubiquitylation and degradation mechanisms.