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Foot-and-mouth disease virus binds αvβ6 integrin, via a conserved RGD motif in the flexible, exposed GH loop of capsid protein VP1, for cell entry. Here Kotechaet al.visualize this interaction with the VP1 GH loop extending away from the viral surface, engaging αvβ6 in an open, active state.

cryoDRGN-ET is a generative neural network method for heterogeneous reconstruction of cryo-ET subtomograms. Using subtomogram tilt-series images, it can capture states diverse in both composition and conformation.

Discovery of new therapeutics has been hampered by the often-limiting resolution and throughput of cryo-EM. Here, the authors determine high-resolution cryo-EM structures of the CDK-activating kinase to establish a methodological framework for the use of cryo-EM in structure-based drug design.

Reoviridae undergo a complex assembly pathway in the host cell. Here the authors use cryo-electron tomography to visualize the assembly stages of mammalian orthoreovirus revealing a single shelled intermediate with gross similarity to an early assembly stage of a family of prokaryotic dsRNA viruses.

Advances in electron cryo-microscopy hardware allow proteins to be studied at atomic resolution.

Lipid membrane fusion is an essential function in many biological processes but little is known about membrane fusion in prokaryotes. The authors here study how haloarchaeal pleomorphic viruses (HRPVs) infect archaeal hosts. The structure-function analysis of the spike proteins shed light on prokaryotic membrane fusion.

The structure of enterovirus 71 in complex with its receptor SCARB2 provides insights into the mechanism of viral uncoating within the endo/lysosome compartment and identifies few conserved key residues within the binding footprint that might facilitate the design of receptor mimic therapeutics.

Foot-and-mouth disease virus (FMDV) capsids are often unstable, thus limiting their use as vaccines. A computational method was used to strengthen protein-protein interfaces and engineer stabilized FMDV capsids, which generated improved antibody responses in vaccinated calves and guinea pigs.

The structure of Aichi virus — a poorly characterized picornavirus that causes severe gastroenteritis in children — shows intermediate features between those of enteroviruses and cardioviruses, and provides clues into its cellular receptor.

Structural studies of the ribosome-associated endoplasmic reticulum translocon complex based on cryo-electron tomography and molecular modelling reveal multiple intermediate states and interactions between the components of the complex and its cofactors.

Allosteric control of metabotropic glutamate receptor is of therapeutic value in the treatment of neurological disorders. Here, using cryoEM, the authors describe the diversity of positive allosteric modulation on the metabotropic glutamate receptor, mGlu₅.

A time-resolved cryogenic electron microscopy analysis provides structural information on the processes of primary and secondary nucleation of tau amyloid formation, with implications for the development of new therapies.

The authors report on the structures of α-synuclein filaments from the brains of individuals with Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies and how they differ from those seen in multiple system atrophy.

Cryo-electron microscopy structures of tau filaments from progressive supranuclear palsy and other tauopathies reveal new filament conformations, and suggest that tauopathies can be classified on several different levels according to their filament folds.

A study using structure determination by cryogenic electron microscopy identifies and characterizes TMEM106B amyloid filaments in human brain, and suggests that their formation is age dependent, with no obvious association with disease.

Cryo-electron microscopy structures are reported in which the full-length human α1β3γ2L GABA_A receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA, and the benzodiazepines alprazolam and diazepam.

Here, the authors provide the structure of mature Coxsackie Virus A10 alone and in complex with its receptor KREMEN1, and of A-particles. This shows how the receptor spans the viral canyon and suggests that receptor binding triggers pocket factor release and conformational changes resulting in expanded particles.

Here, the authors provide cryo-EM structures of mature and immature Spondweni virus, defining the furin recognition site at high resolution, and identifying a lipid that binds E upon capsid maturation and is also present in Zika and Dengue virions.

To date, no therapeutic agents against enterovirus 71, the causative agent of hand, foot and mouth disease, exist. Here, using Cryo-EM Huang et al. characterize two plasmablast-derived plateau-binding neutralizing antibodies conferring effective protection against lethal EV71 challenge in vivo.

Double-shelled bacteriophage φ6 is a well-studied model system used to understand assembly of dsRNA viruses. Here the authors report a near-atomic resolution cryo-EM structure of φ6 and propose a model for the structural transitions occurring in the outer shell during genome packaging.

The Ljungan virus is a picornavirus that lacks the internal coat protein VP4, and the packaging of its RNA genome is poorly understood. Here, the authors use cryo-electron microscopy to visualize this virus and suggest that it uses a different mechanism to other viruses for encapsidation of its genome.

The Cdc45-MCM-GINS (CMG) helicase unwinds DNA during replication, a process that requires the ATPase-dependent activity of the MCM complex. Using cryo-EM reconstructions of the CMG complex in different conformations, the authors propose a model where the N-terminal and AAA+ domains of MCM work in concert to translocate along DNA.

Electron cryomicroscopy can allow the elucidation of macromolecular structures; however, mismatches in symmetry between different components limit the attainable resolution. Here, the authors set out a computational method for extracting and retaining information from such components.

A cryo-EM structure of SARS-CoV-2 ORF3a reveals a new fold conserved in coronaviruses, and functional experiments show ion channel activity that may be important for viral infectivity.

Despite the success of current vaccination against poliomyelitis, safe, cheap and effective vaccines remain sought for continuing eradication effort. Here the authors use plants to express stabilized virus-like particles of type 3 poliovirus that can induce a protective immune response in mice transgenic for the human poliovirus receptor.

A new sample-delivery method for serial X-ray crystallography exploits the full repetition rate of the X-ray free-electron laser at the LCLS facility, thus enabling efficient, high-speed data collection to solve the three-dimensional structures of viruses.

The cryo-electron microscopy structure of the bacteriophage ɸ6 dsRNA genome shows that the genome is packaged in a spooled manner that is more similar to dsDNA viruses than to other dsRNA viruses.

Mendonça et al. determine the structures of both in vitro assemblies of the HIV structural precursor protein Gag and Gag viral-like particles (VLPs) to 4.2 Å and 4.5 Å resolutions, using cryo-electron tomography and subtomogram averaging. This study provides insights into the future development of small molecule inhibitors for HIV-1 infection.