Articles in 2016

Crotonylated lysine residues within histones are linked to transcriptional activation in a process involving histone mark ‘reader’ proteins. Crystallographic analysis of the YEATS domain of the Taf14 protein reveals a mode of crotonylated histone mark recognition via a π-sandwich motif.

The attachment of a nuclear export sequence to the blue light-sensitive LOV2 domain mediates rapid and reversible protein export of the ubiquitin ligase Bre1 with light exposure, resulting in changes in histone ubiquitylation and methylation.

A fluorescent sensor combining a mutated form of the 2-Cys peroxiredoxin Tsa2 unable to undergo thioredoxin-mediated reduction with a redox-sensitive GFP protein allows real-time detection of baseline hydrogen peroxide levels in yeast cells.

A synthetic biochemistry approach optimizes a glucose breakdown pathway to produce acetyl-CoA as a building block for polyhydroxybutyrate bioplastic production in the test tube.

An optogenetic approach using the CRY2−CIB1 heterodimerization system results in light-mediated cross-linking and aggregation of different Rab GTPases, disrupting membrane and endosomal trafficking in various cell types.

Analysis of orphan nonribosomal peptide synthetase–like gene clusters from Aspergillus fumigatus identified a gene cluster responsible for the biosynthesis of fumisoquin isoquinoline alkaloids by amino acid condensation and subsequent tailoring steps reminiscent of plant biosynthetic pathways.

Identification of minimal functional CRY2–CIB1 domains and mutations that increased CRY2 photocycle lifetimes combined with the development of an improved photoactivable Cre recombinase enables efficient gene editing.

A chemical genetic approach to localize human Polo-like kinase 1 (Plk1) to distinct regions along the kinetochore–centromere axis combined with phosphoproteomic analysis reveals the presence of distinct Plk1 pools to mediate chromosomal segregation.

Monitoring new fluorescent ganglioside analogs at a single-molecule level suggests that gangliosides associate dynamically with GPI-anchored protein monomers, transient homodimer rafts, and clustered signaling rafts in a cholesterol-dependent manner.

A combination of shRNA- and CRISPR-Cas9-based gene editing screens, corroborated by a metabolite suppression experiment identifies the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) as the target of the broad-spectrum antiviral compound GSK983.

The use of a selective JAK3 covalent inhibitor reveals two distinct temporal waves of STAT5 phosphorylation. The inhibitor more potently targets the second wave, which is required for cell cycle progression and T cell proliferation.

Activity-based protein profiling identifies AIG1 and ADTRPP as transmembrane threonine hydrolases with substrates that include several fatty acid esters of hydroxyl fatty acids (FAHFAs). New inhibitors of these enzymes inhibit FAHFA hydrolysis.

An approach termed in vivo population quality control, which is coordinated by a metabolite biosensor-survival gene circuit, takes advantage of cell-to-cell variation to optimize production of selected metabolites in isogenic Escherichia coli cultures.

A steric trapping method for monitoring membrane protein folding under native conditions shows an expanded unfolded state of the GlpG intramembrane protease and identifies a network of cooperative interactions at side chain resolution for maintaining its stability.

The development of metabolic tracers reveals that malic enzyme is the main contributor of NADPH production in differentiating adipocytes. During hypoxic conditions, the source of NADPH shifts to the oxidative pentose phosphate pathway.