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Proteome-wide prediction and structural modeling of disordered protein interaction interfaces advance characterization of disease-associated variants in disordered protein regions.
Wilhelm, Pluhackova and colleagues show how ligand binding, receptor phosphorylation and membrane interactions, including PIP2, drive the assembly of human β2-adrenergic receptor–β-arrestin complexes, providing insight into structural mechanisms regulating GPCR signaling.
Vignane et al. show that age-related protein oxidation disrupts normal brain protein organization, promoting harmful condensates and aggregation linked to neurodegeneration, whereas hydrogen sulfide-driven persulfidation counteracts these effects.
Li et al. present cryo-EM structures of the ATR–ATRIP complex bound to the ATR-activating domains of TOPBP1 and ETAA1; these reveal distinct binding modes and allosteric mechanism of activation for TOPBP1 and ETAA1.
Liu, Cai and colleagues show that the human TOM–TIM22 supercomplex acts a translocation unit that directly couples mitochondrial carrier import across the outer and inner membranes, in contrast to the independent function of the complexes in yeast.
Hu et al. identify the secretory phospholipase PLA2G2F as an endoplasmic reticulum-resident ferroptosis suppressor in bladder cancer and provide evidence that PLA2G2F acts on ether-linked phospholipids containing polyunsaturated fatty acids, reducing the pool of these peroxidation-prone phospholipids.
Belleza, Zhang and colleagues showed that the χ-conotoxin χ-AoIA, a venom-derived peptide, reduces pain in mice by blocking the norepinephrine transporter more effectively than other similar peptides.
Using cryo-electron microscopy, Cahill, Hartfield et al. identified six structural states of human acid-sensing ion channel 1a, revealing how acidic conditions and peptide toxins regulate channel activation and desensitization through conformational flexibility.
The authors show that persistent ultrafine DNA bridges become coated by membranes and the ESCRT-III proteins CHMP1B and IST1, which protect the genome within from damage.
Here Thakre, Wang and Liu and colleagues show that the Cdc13–Stn1–Ten1 complex helps cells to repair broken DNA by enabling synthesis of the second DNA strand during break-induced replication, a process important for genome stability and telomere maintenance in some cancers.
Li et al. obtain high-resolution, native structures revealing that cytoplasmic lattices in mammalian eggs organize and store degradative and cytoskeletal complexes for early embryonic development.
Kameswaran et al. show that cancer cells can restore gene expression after TEAD inhibition by shifting control from enhancers to promoters, a process termed ‘promoter reinforcement’, enabling transcription despite disrupted promoter–enhancer communication.
By calibrating Micro-C against live-imaging data in mouse embryonic stem cells, Jusuf et al. quantified 65,929 chromatin loops genome-wide, finding that most loops form pairwise interactions with an absolute probability of only a few percent.
Segura-Bayona et al. uncover genetically separable ATRX functions that independently safeguard telomeres and genome replication, revealing how CST and 9-1-1 pathways suppress accumulation of toxic single-stranded DNA and preserve chromosome integrity.
This study shows that RNA polymerase II traverses overlapping dinucleosomes (OLDNs) with direction-dependent efficiency. Cryo-EM structures further reveal how RNA polymerase II rearranges OLDNs, promoting directional transcription.
The researchers used cryo-electron microscopy to map how synthetic agonists bind to the neurokinin 2 receptor to reveal the features that make them selective. These studies are a key step toward developing future obesity therapies that boost energy expenditure.
Human Argonaute 2 requires distortion of the paired small interfering RNA (siRNA)–target RNA duplex, not just base pairing, to cleave targets. Structures show how RNA shape and key residues enable catalysis, explaining why some siRNAs are more effective.
Cryo-EM structures of AtCas9 bound to underwound minicircle DNA reveal how DNA topology relaxes PAM recognition through topology-dependent interactions, providing a structural basis for near-PAMless CRISPR targeting.
Jiang, Han and Fine and colleagues show that ketamine and phencyclidine can directly bind to and activate opioid receptors. Using structural and pharmacological approaches, they showed how these drugs interact with opioid receptors.
OSTα/β regulates bile acid and steroid conjugate homeostasis. Sun, Tian, Low and colleagues reveal structures of the human OSTα/β transporter, elucidating mechanisms of tetramer assembly, substrate transport and drug inhibition.
