Volume 25 Issue 3, March 2018

Inheritance of Polycomb repressive complex 2 (PRC2)-mediated gene silencing involves self-propagation of histone H3 lysine 27 (H3K27) methylation from an initial nucleation site, but how the first H3K27 methylation marks are established is not fully understood. A recent study reveals that PRC2 can reconstitute H3K27 methylation de novo in cells that have lost the mark. This reconstitution is dependent on the PRC2 core component SUZ12, which provides a novel link between initiation and self-propagation of this critical epigenetic mark.

Nanobodies have emerged as highly versatile and useful binding molecules in biomedical research. A technical report describes a cost- and time-effective in vitro platform that facilitates the generation of desired nanobodies, including conformationally selective nanobodies against agonist-bound G-protein-coupled receptors (GPCRs).

A new study reveals how the oocyte-specific transcription factor TAp63 ensures female germ line fidelity and describes approaches to circumvent premature ovarian insufficiency in women receiving cytotoxic chemotherapy.

Cryo-ET analyses of the microtubule-bound mouse dynein–dynactin complex reveal two dimeric dyneins interacting with the dynactin–cargo adaptor complex, a configuration that can account for processivity and directionality of dynein transport activity.

2′-O-methylation within mRNA coding regions sterically perturbs interactions of ribosomal-monitoring bases with cognate codon–anticodon helices, leading to excessive rejection of cognate aminoacylated tRNAs during initial selection and proofreading.

Crystal structures of human GPT in complex with tunicamycin provide insight into mechanisms of inhibition and differences between human and bacterial enzymes, leading to the design of an analog with specificity for the bacterial enzyme.

Although mechanisms wherein pre-existing H3K27 methylation directs recruitment of PRC2 to support its own maintenance have been proposed, H3K27 methylation patterns in mESCs are not dependent on self-autonomous epigenetic inheritance.

The structure of the minimal GTPase domain of human MFN1 reveals a new, closed conformation and suggests how mitofusin pulls membranes closer to facilitate fusion and how MFN2 mutations impair mitochondria in Charcot–Marie–Tooth neuropathy type 2A.

RNA-directed miRNA degradation triggered by a brain-specific genome-encoded transcript regulates explorative and anxiety-like behavior in zebrafish and affects balance and motor learning in mice.

Structural analyses of Xenopus tropicalis TRPV4 reveal a single ion-binding site in the selectivity filter and distinct interactions between the voltage-sensor-like and pore domains and provide a blueprint to understanding disease-related mutations.

p63 activation in response to DNA damage leads to oocyte death and loss of fertility in women receiving chemotherapy. Activation requires sequential phosphorylation by CHK2 and CK1 kinases, and inhibition of these kinases rescues oocytes from apoptosis induced by chemotherapy.

A platform for high-throughput expression screening and large-scale production of cystine-dense peptides, alongside a global structure-based classification, is presented.

In vivo, in vitro and in silico experiments demonstrate that interface residues of homomeric proteins are enriched toward protein C termini to avoid premature assembly and aggregation.

Yeast surface display platform allows nanobody discovery within two to three weeks. Examples include nanobodies for crystallographic applications, targeting nonpurified antigen or conformationally selective nanobodies to two distinct human GPCRs.