Volume 26 Issue 8, August 2019

On 15 July 2019, the Governor of the Bank of England announced that English mathematician, computer scientist and cryptanalyst Alan Turing will be the new face of the £50 note.

Researchers working on synaptic vesicle fusion and neurotransmitter release share their views on the most interesting developments in their field and the challenges that lie ahead.

The ability of CRISPR-Cas9 to accurately and efficiently target and cleave any segment of double-stranded DNA based solely on the sequence of its loaded guide RNA has revolutionized genome editing. While many structural studies have shed light on the atomic details of DNA targeting, structures of the enzyme poised to perform catalysis have remained elusive. In this issue, Zhu, Clarke, Puppala et al. provide snapshots of the enzyme in action as it performs concerted cleavage of a target DNA¹.

AAA+ ATPase spastin recognizes tubulin polyglutamylated C-terminal tails and severs microtubules. A cryo-EM structure of fly spastin with polyGlu reveals how spastin engages with the substrate, an activity allosterically coupled to nucleotide binding and oligomerization.

Cryo-EM structures of the active Cas9–sgRNA–DNA complex in the presence of Mg²⁺ capture Cas9 in the pre- and postcatalytic states as well as in the product-bound state, and reveal coupled domain motions and interactions between the enzyme and nucleic acids.

Transition metal FRET and Rosetta modeling reveal that the S4 helix in the voltage-sensing domain of the HCN channel moves downward and its carboxy-terminal portion tilts during hyperpolarization activation.

A combination of biochemical, single-molecule, and in vivo assays reveals that the UV-DDB complex that removes UV-induced DNA lesions via the nucleotide excision repair pathway also promotes removal of oxidative lesions via base excision repair.

O-Mannosylation is an essential protein modification implicated in several diseases. Cryo-EM structures of the yeast mannosyltransferase complex Pmt1–Pmt2 bound to substrates reveal the substrate recognition model and confirm the reaction mechanism.

X-ray crystal structures of the full-length TcdB exotoxin of bacterial pathogen Clostridium difficile reveal pH-dependent conformational changes that allow translocation of the toxin from endosomes into the cytosol.

Identification of SFiNX, a complex of Nxf2–Nxt1, a variant of the mRNA export receptor Nxf1–Nxt1 and the Piwi-associated protein Panoramix, demonstrates an RNA export independent role for Nxf2 in piRNA-guided cotranscriptional transposon silencing.

The fly male germline stem cells undergo asymmetric division, with old histones H3 and H4 preferentially retained in the daughter stem cell. The mechanisms that contribute to this outcome are revealed using super-resolution microscopy and DNA fiber analyses.

Comprehensive genome-wide analyses of nucleosome occupancy and promoter activity after rapid depletion of chromatin remodelers in Saccharomyces cerevisiae provides insight into remodeler function in transcription initiation via nucleosome positioning.