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BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

The Ton and Tol systems are bacterial energy-transducing complexes that use the proton motive force at the inner membrane to exert force on outer membrane proteins. Here the authors present the high-resolution cryoEM structures of the inner membrane engine part of these two complexes.

Protein citrullination regulates the physiological function of proteins and is linked to various autoimmune disorders. Here, the authors report on the allosteric targeting of PAD1-4 leading to broad inhibition of protein citrullination in neutrophils.

TRIM5α is an E3 ligase that inhibits retroviral replication. Here, the authors delineate the biochemical mechanism that accelerates N terminal autoubiquitylation of TRIM5α upon its association with the retroviral capsid and, thus, enables recognition of an infection-associated molecular pattern.

Structures of the flagellar MS-ring from Salmonella elucidate its mode of action, revealing how this complex serves as a structural adaptor that enables protein secretion and flagellar rotation.

Cryoelectron microscopy analyses of the counter-clockwise and clockwise states of the Salmonella Typhimurium C-ring reveal the structural bases for changes in rotation of the bacterial flagellum.

Here, the authors present and characterise a collection of human gut bacteria including novel taxa associated with health conditions and a large diversity of plasmids. All isolates, their genomes and metadata are publicly available, facilitating research by others (www.hibc.rwth-aachen.de).

The human ADAR enzyme can deaminate additional transcripts for therapeutic A-to-G RNA base editing using an antisense guide RNA. Here, authors engineer a universal guide RNA scaffold from the U7 snRNA, boosting editing efficiency from minimal doses, especially in organs with limited AAV delivery.

The uptake and elimination of beta-lactam antibiotics are facilitated by the proton-coupled peptide transporters. Here authors present cryo-EM structures of PepT2 in complex with the cefadroxil, amoxicillin and cloxacillin to reveal a mechanism of beta-lactam antibiotic recognition

Here, Arkinson et al. reconstitute NUB1-mediated FAT10 degradation by the human 26S proteasome and use biochemistry, cryo-EM and hydrogen–deuterium exchange to show that NUB1 acts as an ATP-independent chaperone to trap partially folded FAT10 for proteasome delivery.

The transmembrane export apparatus regulates protein secretion through bacterial type III secretion systems. New structural data indicate that MxiA, a major component of the apparatus, assembles in a nonameric ring. This and additional structural information provide a framework for understanding how protein secretion is controlled.

Transcription-coupled repair (TCR) removes DNA lesions from actively transcribed strands. Here, the authors unveil the structural basis for coordinated TFIIH recruitment to the TCR machinery and the role of ubiquitin modifications in directing the response toward DNA repair or proteasomal degradation.

The membrane attack complex is a heteromeric assembly of complement proteins where multiple copies of C9 are recruited by the C5b678 complex to form lytic pores in pathogen membranes. Here the authors present the structure of a soluble pore-like form of the C9 component that reveals details of the oligomerization interfaces.

The poly(ADP-ribosyl)transferases, tankyrase 1 and 2, are regulated by RNF146-mediated K48-linked polyubiquitylation and degradation. Here the authors show that this is opposed by K11-linked diubiquitylation by RING-UIM E3 ligases RNF114 and 166 and further impacted by several PAR-binding E3 ligases.

Endosomal biogenesis is vital for eukaryotic cell physiology and relies on membrane fusion promoted by the CORVET tethering complex. Here, the authors solved the structure of CORVET by cryo-EM and reveal its minimal requirements for membrane tethering.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

The bacterial anti-phage defense systems known as ‘Zorya’ consist of a membrane protein complex (ZorAB) and soluble components of unclear function. Here, the authors solve cryo-EM structures of the ZorAB complex and show that the soluble component ZorE displays nickase activity and acts as an effector module.

Widespread grassland degradation poses major societal and environmental challenges. Here, the authors propose multiple targeted interventions as a crucial strategy for simultaneously enhancing grassland ecosystem services and improving their equitability.

Streptomyces bacteria undergo two modes of cell division: formation of cross-walls in hyphae, leading to multicellular compartments, and septation for release of unicellular spores. Here, Bush et al. identify a protein that is important for both cell division modes in Streptomyces, likely by contributing to stabilization of the divisome.

Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.

The in situ cryo-electron microscopy structure of the intact Salmonella flagellar basal body—including the inner membrane rotor, drive shaft and outer membrane bushing complex—elucidates the mechanisms of assembly of this complex macromolecular structure that enables bacterial motility.

Spectral Denoising removes chemical and electronic noise from mass spectrometry data to improve metabolite annotation.

Using single-particle analysis cryogenic electron microscopy, the authors determine the structures of the bacterial flagellum stator complexes from three diverse bacteria.

Uncertainty associated with solution-based electron-transfer studies of DNA–metal-complex systems has now been overcome by combining X-ray and time-resolved infrared data obtained for ruthenium polypyridyl–DNA crystals. Using these methods both the geometry of the reaction site and the kinetics of the reversible photo-induced one-electron oxidation of guanine have been determined.

Devising a total synthesis of the anti-cancer drug taxol has engaged the attention of chemists for more than 20 years. But their ingenuity — and perseverance — has been rewarded.

Macrophage-expressed gene 1 (MPEG1) functions within the phagolysosome to damage engulfed microbes, presumably via forming pores in target membranes. In order to provide insights into the mechanism of MPEG1 function and membrane binding, the authors present structures of hexadecameric MPEG1 prepores both in solution and in complex with liposomes.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

The enzymes and pathway involved in the biosynthesis of coenzyme F₄₃₀ are identified, completing our understanding of how members of the cyclic modified tetrapyrrole family are constructed.

Gram-negative bacteria use type III secretion systems (T3SSs) to pass virulence factors into host cells, making them potential therapeutic targets to combat bacterial infection. A new EM study of the needle complex from the Shigella T3SS reveals 12-fold symmetry throughout and suggests interactions important for self-assembly and complex stability.

This work reveals the structural and biochemical basis for phosphorylation-dependent day/night signaling by KaiC in the cyanobacterial circadian clock.

Cryo-EM structure of the Salmonella Typhimurium FliP–FliQ–FliR complex identifies this export gate as a core component of the periplasmic portion of the type III secretion system.

Artemisinin-resistantPlasmodium is an increasing problem. Here, using a medicinal chemistry programme, the authors identify a tetraoxane-based drug candidate that shows no cross-resistance with an artemisinin-resistant strain (PfK13-C580Y) and is efficient in Plasmodiummouse models.

Bayesian analysis of fluorophore blinking and bleaching in image data collected from simple xenon arc lamp illumination and high-speed wide-field imaging of standard fluorescent proteins allows localization microscopy in living cells with a 50 nm spatial and a 4 s temporal resolution.