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The adhesion complex (Nap) in Mycoplasma genitalium is composed of the adhesin proteins P110 and P140 and essential for infectivity, motility and adhesion of this human pathogen. Here, the author present the structures of P140 alone and the P140/P110 complex in closed and open conformations and based on their structural data and further functional studies propose a mechanism for the attachment and release of M. genitalium to the host cell receptor.

Structural and biochemical analyses of human USP30 explain the basis of Lys6-linkage preference and regulation by PINK1 and Parkin, shedding light onto how USP30 can act as a brake on mitophagy.

Rules that allow the design of strongly funnelled protein folding energy landscapes by relating secondary structure patterns to protein tertiary motifs are used to produce ideal protein structures stabilized by completely consistent local and non-local interactions.

Leucine-rich repeats (LRRs) can form horseshoe-like structures with different curvatures in nature. A computational approach now allows the design of 12 new LRR proteins with precise curvatures, using defined building blocks and junction modules.

Cytokinetic abscission relies on the local constriction after cytoskeleton disassembly, but it is not known how the actin filaments are disassembled. Here, the authors show that the redox enzyme MICAL1 is recruited by Rab35 and induces oxidation-mediated depolymerization of actin, which is required to recruit ESCRT-III and complete abscission.

Wyatt et al. explore glycaemic responses after a standardized meal and find that postprandial glycaemic dip is a predictor of hunger and subsequent energy intake.

Photoreceptor proteins utilise biological chromophores to regulate a large range of cellular processes in response to light. Here the authors identify and characterise a sub-family of multi-centre photoreceptors, termed photocobilins, that not only utilise B₁₂ but also contain biliverdin (BV) as an additional chromophore.

CarH is a bacterial B₁₂-binding photoreceptor involved in transcriptional regulation. Here, the authors provide insights into B₁₂ dynamics and associated cobalt redox changes following light activation. These demonstrate the CarH response integrates light and oxygen sensing.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Crystal structures of human O-GlcNAc hydrolase (hOGA) fragments show that hOGA's dimeric structure is organized by swapping of an α-helical element and reveal features of inhibitor binding to the catalytic domain.

This paper shows that the effects of amyloid-beta oligomers on long-term potentiation are mediated by the cellular prion protein — notorious for its involvement in diseases such as bovine spongiform encephalopathy, new variant Creutzfeldt–Jakob disease and kuru.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Computationally designed icosahedral protein-based assemblies can protect their genetic material and evolve in biochemical environments, suggesting a route to the custom design of synthetic nanomaterials for non-viral drug delivery.

Pathogen triggered N-terminal degradation of NLRP1 and CARD8 by the proteasome releases their C-terminal UPA-CARD fragments (CT) to form the inflammasome, which in turn activates caspase-1. Here, the authors present the cryo-EM structures of the NLRP1-CT and CARD8-CT helical filaments as well as the ASC⁻caspase-1 octamer structure, which together with in vitro and cell based assays provide further insights into the architecture and specificity of the active NLRP1 and CARD8 inflammasomes.

A library of fluorogenic dyes enables the measurement of protein unfolding for a large range of proteins.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Small-angle X-ray and neutron scattering are used to extract structural parameters and derive structural models of macromolecules in solution. The preparation of pure, monodisperse samples and exactly matching solvent blanks is crucial to the experiments' success.

Fluorescent protein reporters based on GFP exist, but have intrinsic disadvantages. Here the authors incorporate pH, Ca²⁺ and protein–protein interaction sensing modalities into de novo designed mini-fluorescence-activating proteins (mFAPs), with increased photostability and smaller size, which bind a range of DFHBI chromophore variants.

Nebulized mRNA delivery has broad therapeutic potential but has proven challenging. Here, the authors report on a modified lipid nanoparticle with improved conditions to allow nebulization and demonstrate its application for delivering mRNA to the lungs.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Next-generation lipid nanoparticles that target non-hepatocytes could be important clinical tools. Using in vivo DNA barcoding, the authors identify piperazine-containing lipids deliver mRNA to immune cells without targeting ligands.

The delivery of oligonucleotides disrupting the secondary structure of single-guide RNAs and of short interfering RNAs targeting Cas9 mRNA can enhance lipid-nanoparticle-mediated gene editing in vivo in tissues other than the liver.

The condensation of RNA polymerase II (Pol II) into transcriptionally active clusters is critical for eukaryotic gene regulation and pre-mRNA transcription. Here the authors show that a tight network of tyrosine-proline interactions imparts temperature and concentration-dependent self-coacervation of Pol II’s C-terminal domain (CTD).

HDAC6 is a tau deacetylase and acetylation of tau inhibits its function and promotes aggregation. Here the authors show that HDAC6 protects against tau accumulation in a mouse model of tauopathy.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Multiple scattering complicates femtosecond optics such that phase conjugation allows spatial focusing and imaging through a multiple scattering medium, but temporal control is problematic. McCabeet al. report the full spatio-temporal characterization and recompression of a femtosecond speckle field.

Structural insights demonstrating small-molecule-mediated dimerization of BRD4 bromodomains led to the development of biBET, a compound that potently inhibits BRD4–acetyl-lysine interactions by bivalent binding to tandem bromodomains.

A high-throughput method leveraging peptide-encoding mRNA barcodes for the in vivo screening of libraries of nanoparticle formulations allows for the rapid optimization of a lipid nanoparticle for the delivery of mRNA to the liver.

The computational design of an extremely stable icosahedral self-assembling protein nanocage is presented; the icosahedron should be useful for applications ranging from calibrating fluorescence microscopy to drug delivery.

A hyper-stable de novo protein mimic of interleukin-2 computationally designed to not interact with a regulatory T-cell specific receptor subunit has improved therapeutic activity in mouse models of melanoma and colon cancer.

In retroviruses, the capsid protein (CA) forms a shell surrounding the viral core. Here the authors combine cryo-electron microscopy with NMR and X-ray crystallography to examine the CA structure from the human endogenous retrovirus HML2 (HERV-K) and determine the structures of four Fullerene CA closed shells that reveal the molecular basis of capsid assembly.

The conversion of auditory and vestibular stimuli into electrical signals is initiated by force transmitted to a mechanotransduction channel through the tip link. Here authors show that a single tip-link bond is more mechanically stable relative to classic cadherins, and that the double stranded tip-link connection is stabilized by single strand rebinding facilitated by strong cis-dimerization domains.

Sun et al. has studied the genetically encodable halotyrosines in proteins of the prokaryotic cell division machinery to elucidate the general role of halogenation in cellular lifespan and oxidative damage-induced diseases such as aging and cancer.

A computational approach is used to design modular proteins that bind to synthetic peptides and disordered regions of human proteins with high affinity and specificity.

Staphylococcal biofilm formation is promoted by the surface protein SasG. Here, the authors characterize the structure and remarkable mechanical strength of the repeat region of SasG, and show how elongation is achieved by obligate folding of the disordered regions within the repeating units.

The transportation of large molecules through the vascular endothelium presents a major challenge forin vivodrug delivery. Here, the authors demonstrate the potential of using external magnetic fields and magnetic nanoparticles to enhance the local extravasation of circulating large molecules.

Typically, ion conducting polymers exhibit a trade-off between mechanical robustness and ionic conducting performance. Here, the authors utilize supramolecular chemistry obtaining extremely tough electrolytes with high ionic conductivity and enabling stretchable lithium-ion batteries.

Radionuclide brachytherapy delivered via an injectable biopolymer depot conjugated with iodine-131 and combined with systemically delivered paclitaxel induced the complete regression of multiple subcutaneous and orthotopic pancreatic tumours in mice.