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Current understanding of the structure of Dicer is restricted to simple forms of the enzyme from lower eukaryotes or isolated domains from higher eukaryotic Dicers. A new domain localization strategy was developed to determine the structure of human Dicer by EM, revealing the structural basis for small RNA production in eukaryotes.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

A standardized, realistic phantom dataset consisting of ground-truth annotations for six diverse molecular species is provided as a community resource for cryo-electron-tomography algorithm benchmarking.

Time-resolved cryo-EM captured transient intermediates during E. coli RNAP promoter melting, revealing conformational changes affecting stepwise transcription bubble opening. Results inform how DNA sequence controls bacterial transcription initiation.

Reducing the length of time that protein particles spend on a sample grid prior to freezing mitigates deleterious effects caused by particle adsorption to the air–water interface in single-particle cryo-EM.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Two cryo-electron-microscopy images of the histone chaperone FACT interacting with components of nucleosomes shed light on how FACT manipulates nucleosomes to promote transcription, DNA repair and DNA replication.

The cryo-EM structure of Mycobacterium smegmatis arabinosyltransferase B EmbB involved in mycobacterial cell wall biosynthesis provides insights into the substrate binding and reaction mechanism. Mapping of the ethambutol resistance associated mutations onto the structure suggests the location of the drug binding site.

Designed β-strand peptides stabilize integral membrane proteins for biochemical and structural studies, enabling electron microscopy analysis of the dynamic conformations of the ABC transporter MsbA.

Here the authors describe the Waffle Method, aimed at increasing the throughput of and solves several challenges present in cryo-FIB/SEM sample preparation for cryo-ET analysis — the highest-resolution method for obtaining 3D views of native biological specimens in-situ.

APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

Presequence protease (PreP) is essential to mitochondrial proteostasis. This study leverages advanced vitrification techniques to solve cryoEM structures of apo- and substrate-bound PreP and integrates these data with other analysis to reveal key stages and mechanistic insights of the PreP catalytic cycle.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Structural, functional and in silico analyses of the chloroquine-resistance transporter PfCRT of Plasmodium falciparum suggest that distinct mechanistic features mediate the resistance to chloroquine and piperaquine in drug-resistant parasites.

An alternative HIV vaccine design facilitates generation of HIV-1-antibodies, with promising neutralization breadth in rodents and nonhuman primates.

G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins in humans and exhibit diverse activation mechanisms. Here, the authors combine electron microscopy, hydrogen deuterium exchange and Molecular dynamics simulations to gain insight into the activation mechanism of the glucagon receptor.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

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.

Cryo-EM analyses of the initial contact of the HIV-1 Env trimer with the CD4 receptor reveal that CD4 interacts with two gp120 protomers; these quaternary contacts are important for viral infectivity.

A spraying-mixing approach for preparing cryo-EM grids using the Spotiton robot allows time-resolved observations of short-lived biomolecular states.

Clustered protocadherin ectodomains spontaneously assemble to form a zipper-like lattice of alternating cis and trans interactions at membrane contact sites, which probably represents their mode of function in neuronal self-recognition.

Cryo-electron microscopy structures of insulin in a complex with the insulin receptor define the S2 binding site on the receptor and suggest a mechanism for downstream propagation of insulin signalling.

The preferred specimen orientation problem limits accuracy and resolution in structure determination by cryo-EM. Collecting data at defined sample tilts yielded near-atomic-resolution structures for the influenza hemagglutinin trimer and ribosomal biogenesis intermediates.

David Whitcomb, Bernie Devlin and colleagues report the results of a genome-wide association study of pancreatitis. They identify common variants at two loci associated with risk of this disease, including one on the X chromosome that shows strong evidence of interaction with alcohol consumption.