Volume 29 Issue 4, April 2022

The CRISPR–Cas enzyme Cas9 faces the challenge of identifying a specific nucleotide sequence within double-stranded DNA. New cryo-EM and biochemical studies show that in the earliest steps of binding, Cas9 bends the DNA and promotes unwinding of two base pairs, enabling it to efficiently scan the sequence of this critical region.

Cryo-EM analysis reveals the mechanism by which chromatin is compacted at the centromere by the H3 histone variant CENP-N. Intriguingly, despite the structural differences between CENP-N and linker H1 histones, both appear to similarly compact higher-order nucleosome structures.

DOPEGAL, a metabolite of norepinephrine in the locus ceruleus, covalently modifies tau and accelerates its aggregation and propagation, leading to cognitive deficits in Alzheimer’s disease.

Comprehensive functional and structural probing of the HIV-1 5′ untranslated region reveals novel interactions that regulate RNA dimerization, Pr55Gag binding and genome packaging into virions.

NMR shows that ATP- and ADP-actin differ globally, including ground and excited state structures and dynamic architecture. Analyses of an actin mutant suggest the high-energy conformer of ATP-actin may be on the pathway to filament nucleation.

Biochemical and cell-based assays reveal that PARP inhibitors impede the maturation of nascent DNA strands during DNA replication, and implicate unligated Okazaki fragments and other nascent strand discontinuities in the cytotoxicity of these anti-cancer compounds.

Cryo-EM structures of the AP2 clathrin adaptor complex describe a new checkpoint in the formation of clathrin vesicles and reveal how a conserved family of regulators called muniscins couple the initial recruitment of AP2 with downstream cargo engagement

Cryo-EM analysis reveals that human PTase α/β subunit has a well-ordered catalytic core and flexible peripheral domains that contain a hockey stick-like motif, which moves in and out of the catalytic pocket to control the enzyme activation.

Through structural and functional analyses, this work defines the molecular mechanisms underlying the activation of the insulin receptor (IR) involving multisite insulin binding, paving the way for the eventual therapeutic intervention for diseases caused by aberrant activation of IR.

Cryo-EM structures of the yeast 9-1-1 checkpoint clamp in complex with the Rad24-RFC clamp loader and a DNA substrate explain how 9-1-1 is recruited to DNA junctions with recessed 5′ ends and reveal the mechanism of sliding clamp loading.

Cryo-EM analysis reveals that the 9-1-1 clamp loader Rad24-RFC recognizes the 5′-recessed DNA end. The Rad24 subunit holds the DNA above the clamp, thereby loading the 9-1-1 clamp in the opposite direction of RFC loading DNA into the PCNA clamp.

Here the authors reveal the structural basis of how the nicotinic acetylcholine receptor type found on skeletal muscle and in fish electric organs desensitizes in response to agonist and how the arrow poison curare antagonizes the channel by stabilizing a desensitized state.

Here, the authors use cryo-EM and biochemical analysis to investigate how the CRISPR-associated protein Cas9 interrogates DNA to locate its RNA-matching target sequence.

Cryo-EM and biochemical analyses reveal that centromere-associated protein CENP-N promotes centromere-specific nucleosome stacking and higher order structures in vitro and in the cell.