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This protocol describes procedures for the high-throughput in situ X-ray screening of and data collection from soluble and membrane-protein crystals at room temperature and under cryogenic conditions using Mylar-based film sandwich plates.

A method for de novo design of peptide macrocyles called RFpeptides has been developed. RFpeptides is an extension of RoseTTAFold2 and RFdiffusion and combines structure prediction and protein backbone generation for rapid and custom design of macrocyclic peptide binders.

Pentatricopeptide repeat (PPR) proteins bind RNA and control diverse aspects of RNA metabolism in eukaryotic cells. Here, Coquille et al.present the crystal structures of several engineered PPR domains, elucidate their RNA binding mode and suggest paths to the design of modular, sequence-specific PPR domains.

The structure of the GABA_B receptor in an inactive state reveals, amongst other features, a latch between the two subunits that locks the transmembrane domain interface, and the presence of large phospholipids that may modulate receptor function.

Structures of 5-lipoxygenase (5-LOX) reveal that NDGA disturbs regions that shield the active site while AKBA binds an allosteric site. NDGA inhibits 5-LOX activity using its redox-active function, while AKBA changes the enzyme’s regiospecificity

Post-fast refeeding increases intestinal stem cell function and tumour formation by augmenting protein synthesis via polyamine metabolism.

Nitrogenases are of high interest due to their ability to form NH₄⁺ by reduction of atmospheric dinitrogen. However, the detailed architecture of the Fe-only isoform remained unknown. Now, a high-resolution crystal structure of Fe-nitrogenase is solved, deepening the understanding of nitrogenase catalysis.

CtBP is a transcriptional master co-repressor with oncogenic activity. Here, the authors use structural and biophysical methods to show that CtBP interacts with RAI2 through SLiMs that induce CtBP polymerization and inactivation.

The T cell receptor β-chain is expressed in two isoforms, TRBC1 and TRBC2, with clonally expanded mature T cell lymphomas expressing one of them exclusively, while healthy T cells randomly express either TRBC1 or TRBC2. Here authors show structure-based design of a TRBC2-specific antibody, and depletion of malignant T cells carrying TRBC1 or TRBC2 with CAR-T cells against the cognate receptor chain in murine models.

Sarcoma is a highly heterogeneous disease, which can be caused by a large variety of mutations. Here, the authors utilise multi-omics to characterise a cohort of 1,340 sarcoma tissue specimens to identify key somatic mutations and identify immune subtypes.

The transfer of a phosphate group from a CDP-linked donor to an acceptor alcohol is catalysed by CDP-alcohol phosphotransferases. Here, Sciara et al. report crystal structures of a CDP-alcohol phosphotransferase, define roles of conserved residues and propose a mechanism of action for this protein family.

CDP-alcohol phosphotransferases (CDP-APs) are critical for the biosynthesis of glycerophospholipids. Here, Clarke et al.present the first structure of an enzymatically active CDP-AP in the presence of a bound lipid substrate and propose a mechanism for substrate binding and catalysis.

The [Mo:7Fe:9S:C] iron-molybdenum cofactor (FeMoco) of nitrogenase is a large metal cluster with an important role in biological nitrogen fixation. Here, the authors use spatially resolved refinement of the anomalous scattering contributions of the iron atoms to determine the resting-state electron distribution of FeMoco.

[2Fe-2S] protein cofactors are essential for life and are synthesized on ISCU2 scaffolds. Here, the authors show that hydrophobic interaction of two conserved N-terminal tyrosines induces ISCU2 dimerization and concomitant [2Fe-2S] cluster synthesis.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Structural and biochemical studies of an acetyltransferase demonstrate that conformational changes differ depending on the ligand bound, indicating that binding cooperativity is more complex than expected.

Rad50 is an ABC-type ATPase that forms a complex with the nuclease Mre11 and plays an essential role in the signaling and repair of DNA damage. Now crystal structures and SAXS analyses, along with functional assays, reveal how Rad50 transmits information between the ATPase and Mre11-binding sites, and the mechanism uncovered may be general to other ABC ATPases.

Nectins and nectin-like proteins promote intercellular adhesion and tissue patterning in vertebrates through homophilic or heterophilic interactions. Now the formation of all the possible nectin pairs is studied systematically in vitro, and crystal structures provide insight into the molecular basis for the adhesive binding specificity of nectins.

G protein-coupled receptors are a large family of signalling proteins that mediate cellular responses primarily via G proteins or arrestins, and they are targets of one-third of the current clinically used drugs; here, an active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin-1 is determined, revealing unique structural features that may constitute essential elements for arrestin-biased signalling.

The genetic basis of clear cell sarcomas of the kidney is not well understood. In this study, Roy et al. perform whole-exome and RNA sequencing of these tumours and identify recurrent internal tandem duplications in BCOR, a key constituent of a variant polycomb repressive complex.

Genetic heterogeneity and clonal evolution contribute to cancer progression. Here Ma et al.use deep whole-exome sequencing to identify recurrently mutated pathways and clonal architecture in pediatric acute lymphoblastic leukaemia, shedding light on the evolutionary trajectory from diagnosis to relapse

Wilms tumour is a rare renal neoplasm that primarily affects children but the genomic changes responsible for its development are currently largely unknown. In this study, the authors identify somatic mutations of the MLLT1gene that are potentially involved in the aetiology of a subset of Wilms tumours.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

Boron nitride nanotubes (BNNTS) have only been shown to dissolve in chlorosulfonic acid (CSA) at low concentrations. Here the authors successfully demonstrate the formation of liquid crystals of BNNTs in CSA that can be used to produce macroscopically aligned neat fibers of BNNTs.

Elizabeth Perlman and colleagues use genome-wide sequencing, RNA expression, DNA copy number and methylation analyses to characterize the genomic landscape of Wilms tumors. Their integrated analyses implicate two major classes of genetic changes in Wilms tumors that preserve the progenitor state and/or interrupt normal kidney development.

The X-ray crystal structure of NapA, a Na⁺/H⁺ antiporter from Thermus thermophilus, in an active, outward-facing state is reported; comparisons to the structure of a related transporter in a low pH/inactivated, inward-facing state show the conformational changes that occur when the membrane protein moves from an inward-facing to an outward-facing state, suggesting that Na⁺/H⁺ antiporters operate by a two-domain rocking bundle model.

Sulfite-reducing microbes couple the reduction of sulfite to the generation of a proton motive force that sustains organismic growth; here, two X-ray crystal structures are solved of MccA, a c-type cytochrome enzyme with eight haem groups that catalyses the six-electron reduction of sulfite to sulfide at a novel haem–copper active site.

Physical mapping of DNA can be used to detect structural variants and for whole-genome haplotype assembly. Here, the authors use CRISPR-Cas9 and high-speed atomic force microscopy to ‘nanomap’ single molecules of DNA.

Vicinity of small bodies might be dangerous to the spacecrafts and to their instrumentation. Here the authors show the operational environment of asteroid Bennu, validate its photometric phase function and demonstrate the accelerating rotational rate due to YORP effect using the data acquired during the approach phase of OSIRIS-REx mission.

Bennu’s surface has experienced continuous changes, mostly induced by its accelerating spin rate, which could have resulted in a collapse of its interior in the past. This scenario is also supported by the heterogeneity of Bennu’s internal mass distribution.

Bennu’s surface presents evidence of a variety of particle sizes, from fine regolith to metre-sized boulders. Its moderate thermal inertia suggests that the boulders are very porous or blanketed by thin dust. Bennu’s boulders exhibit high albedo variations, indicating different origins and/or ages.

Signatures of phyllosilicate-like hydrated minerals are widespread on Bennu’s surface, indicating significant aqueous alteration. The lack of spatial variations in the spectra down to the scale of ~100 m indicates both a relatively uniform particle size distribution and a lack of compositional segregation, possibly due to surficial redistribution processes.

Near-Earth rubble-pile asteroid Bennu has an unexpectedly old surface, with numerous candidate impact craters and morphologically diverse boulders, according to early observations by the OSIRIS-REx mission.

Near-Earth asteroid Bennu has a top-like shape with longitudinal ridges, macroporosity, prominent boulders and surface mass wasting, suggesting that it is a stiff rubble pile, according to early observations by the OSIRIS-REx mission.

Observations of asteroid (101955) Bennu with NASA’s OSIRIS-REx spacecraft reveal an unexpected surficial diversity that poses a challenge to the success of the sample-return mission.